gebhart/patrepeval huggingface dataset:
A shortcut to high-affinity Ga-68 and Cu-64 radiopharmaceuticals: one-pot click chemistry trimerisation on the TRAP platform (2015)

Due to its 3 carbonic acid groups being available for bioconjugation, the TRAP chelator (1,4,7-triazacyclononane-1,4,7-tris(methylene(2-carboxyethylphosphinic acid))) is chosen for the synthesis of trimeric bioconjugates for radiolabelling. We optimized a protocol for bio-orthogonal TRAP conjugation via Cu(I)-catalyzed Huisgen-cycloaddition of terminal azides and alkynes (CuAAC), including a detailed investigation of kinetic properties of Cu(II)-TRAP complexes. TRAP building blocks for CuAAC, TRAP(alkyne)3 and TRAP(azide)3 were obtained by amide coupling of propargylamine/3-azidopropyl-1-amine, respectively. For Cu(II) complexes of neat and triply amide-functionalized TRAP, the equilibrium properties as well as pseudo-first-order Cu(II)-transchelation, using 10 to 30 eq. of NOTA and EDTA, were studied by UV-spectrophotometry. Dissociation of any Cu(II)-TRAP species was found to be independent on the nature or excess of a competing chelator, confirming a proton-driven two-step mechanism. The respective thermodynamic stability constants (log K(ML): 19.1 and 17.6) and dissociation rates (k: 38 × 10(-6) and 7 × 10(-6) s(-1), 298 K, pH 4) show that the Cu(II) complex of the TRAP-conjugate possesses lower thermodynamic stability but higher kinetic inertness. At pH 2-3, its demetallation with NOTA was complete within several hours/days at room temperature, respectively, enabling facile Cu(II) removal after click coupling by direct addition of NOTA trihydrochloride to the CuAAC reaction mixture. Notwithstanding this, an extrapolated dissociation half life of >100 h at 37 °C and pH 7 confirms the suitability of TRAP-bioconjugates for application in Cu-64 PET (cf. t(1/2)(Cu-64) = 12.7 h). To showcase advantages of the method, TRAP(DUPA-Pep)3, a trimer of the PSMA inhibitor DUPA-Pep, was synthesized using 1 eq. TRAP(alkyne)3, 3.3 eq. DUPA-Pep-azide, 10 eq. Na ascorbate, and 1.2 eq. Cu(II)-acetate. Its PSMA affinity (IC50), determined by the competition assay on LNCaP cells, was 18-times higher than that of the corresponding DOTAGA monomer (IC50: 2 ± 0.1 vs. 36 ± 4 nM), resulting in markedly improved contrast in Ga-68-PET imaging. In conclusion, the kinetic inertness profile of Cu(II)-TRAP conjugates allows for simple Cu(II) removal after click functionalisation by means of transchelation, but also confirms their suitability for Cu-64-PET as demonstrated previously (Dalton Trans., 2012, 41, 13803).
Functional screening using a microRNA virus library and microarrays: a new high-throughput assay to identify tumor-suppressive microRNAs (2010)

MicroRNA (miRNA) is a class of non-coding RNAs that represses expression of target messenger RNAs posttranscriptionally. A growing body of evidence supports their roles in various normal cellular processes, as well as in pathological conditions, such as cancer. We established a functional screening assay that enables high-throughput identification of miRNAs that have a role in cancer phenotypes of interest, via the combination of pooled lentivirus vectors expressing several hundred miRNA precursors and a custom-made microarray. Self versus self-hybridization analysis using pooled polymerase chain reaction products generated highly linear and reproducible results. To test the feasibility of the assay, we focused on miRNAs that control proliferation of pancreatic cancer cells and successfully identified five miRNAs that negatively control cell proliferation, including miRNA-34a that was previously identified as a representative tumor-suppressive miRNA. The results were further validated using lentivirus vectors expressing each of the five miRNAs or synthetic miRNAs. The function-based nature of the assay enabled identification of miRNAs that were strongly linked to cell proliferation, but the relative ease and flexibility of the assay allow for future studies of cancer stem cells, metastasis and other cancer phenotypes of interest.
Cultivar-Specific Elicitation of Barley Defense Reactions by the Phytotoxic Peptide NIP1 from<i>Rhynchosporium secalis</i> (1993)

Resistance of barley to the phytopathogenic fungus, Rhynhosporium secalis race US238.1, was found to be controlled by resistance gene Rrs1, which segregated in a manner characteristics for a codominant gene. PRHv-1, a thaumatin-like pathogenesis-related protein, was shown to be encoded by a gene family on chromosome 1. As part of the barley defense response, significant accumulation of PRHv-1 and peroxidase transcripts was induced early during pathogenesis in two Rrs1 cultivars but not or to a lower level in a near-isogenic, susceptible rrs1 cultivar or a cultivar lacking known resistance genes. R. secalis secretes a small group of necrosis-inducing peptides. One of these, NIP1, which was detected in culture filtrates only of fungal race US238.1, was found to elicit the accumulation of PRHv-1 and peroxidase mRNAs in Rrs1 cultivars with a time course similar to that upon fungal infection. Therefore, NIP1 is a candidate for the product of fungal avirulence gene avrRrs1, which, together with barley resistance gene Rrs1, determines incompatibility of the interaction.
Metazen – metadata capture for metagenomes (2014)

Metazen is an interactive tool that aids users in recording their metadata in a complete and valid format. A defined set of mandatory fields captures vital information, while the option to add fields provides flexibility.
Pathophysiology of Chronic Migraine and Mode of Action of Preventive Medications (2011)

Evidence has accumulated in recent years indicating structural, physiologic, and biochemical alterations in the brain of patients with chronic migraine (CM). Altered pharmacologic responses to opioids and other analgesics have also been reported. Structural or morphologic changes include reduced cortical gray matter of the pain processing areas of the brain and iron accumulation in the periaqueductal gray matter (PAG), red nucleus, and basal ganglia structures. These changes correlate with the duration of migraine disorder and, therefore, are more marked in CM compared to episodic migraine (EM). A dysmodulation of trigeminovascular nociception resulting from changes in PAG may be an important factor in the pathophysiology of CM. Even though the pathophysiology and significance of subcortical white matter lesions and infarct like cerebellar lesions are not fully understood, their occurrence in patients with frequent migraine is further evidence of structural alterations in the brain in CM. Physiologic changes in CM are altered brain metabolism, excitability, and central sensitization of nociceptive pathways. CM is associated with alterations in the brain metabolism confirmed by positron emission tomography (PET) studies. Of special interest is the reversible hypometabolism in the insula, thalamus, anterior cingulate, and parietal lobe and sustained hypometabolism in the orbitofrontal cortex in medication overuse headache. Cortical excitability is increased in CM compared to EM, as confirmed by magnetic suppression of visual accuracy. Cutaneous allodynia, which is more often seen in CM, is a marker of central sensitization. Central sensitization generates free radicals that damage PAG. Cutaneous allodynia is correlated with frequency of migraine attacks and duration of migraine illness. Chronically sensitized central nociceptive neurons may account for CM and its resistance to treatment. Alterations in central glutamate neurotransmission have been reported in the anterior cingulate and insula using magnetic resonance spectroscopy. Medications affecting central glutamatergic neurotransmission may have a potential therapeutic role in CM. Frequent use of opioids and analgesics in EM leads to CM. Opioid-induced hyperalgesia, recognized in recent years, can lead to intractability of migraine. Better understanding of the pathophysiology of CM should lead to better ways to treat these patients. The various effective preventive agents used in migraine prophylaxis, such as topiramate, valproate, β-blockers, and tricyclic antidepressants, appear to have a common effect of suppressing cortical excitability (cortical spreading depression). Suppression of cortical spreading depression by these agents is correlated with the dosages and the duration of treatment. The beneficial effect of botulinum toxin in CM may be due to its antinociceptive effect. Changes in the glutamate and calcitonin gene-related peptide at the peripheral nerve endings reduce peripheral sensitization, which eventually leads to reduced central sensitization.
Fast and Regioselective Heck Couplings with <i>N</i>-Acyl-<i>N</i>-vinylamine Derivatives (2005)

Highly regioselective Heck couplings of aryl triflates with N-acyl-N-vinylamines lacking an N-alkyl substituent were achieved with reaction times of approximately 1 h in yields ranging from 62 to 98% using 1.5 mol % of Pd(2)(dba)(3), 3 mol % of DPPF, and diethylisopropylamine in dioxane. The efficiency of these cross-couplings were studied with several N-vinylamides and an example each of an N-vinylcarbamate and an N-vinylurea. The Heck coupling products easily underwent acidic hydrolysis to the corresponding aryl methyl ketone or in situ hydrogenation in the presence of (Ph(3)P)(3)RhCl under a hydrogen atmosphere to provide the N-acyl derivatives of pharmaceutically relevant benzylic amines. The coupling of a vinyl triflate and more interestingly a vinyl tosylate to N-vinyl acetamide was also studied affording a 2-acylamino-1,3-butadiene with the same high regioselectivity in preference for the alpha-isomer. This result suggests that Heck couplings of electron-rich alkenes with vinyl tosylates also follow a cationic pathway.
A Numerical Analysis of Unsteady Flow in Kojima Lake (2000)

We study unsteady flow that models lake flow in Kojima Lake. We assume that a lake is connected to another area with gates, and that those gates are opened when the water level outside the gates is lower than the water level of the lake. We study unsteady flow due to the opening of the gates. We analyze the problem with the finite element method, and take detailed structures of the gates into account.
Composition of the surface waxes of apple fruits and changes during storage (1973)

Abstract The hydrolysed surface waxes of Dougherty, Granny Smith and Sturmer apples at harvesting consisted of 57 to 62% acids, 21 to 26% hydrocarbons, 7% primary alcohols, 3 to 5% secondary alcohols and 4 to 7% of other constituents. The hydrocarbon homologues ranged from C 18 to C 31 with n ‐nonacosane comprising 84 to 92% of the total hydrocarbons. The primary alcohols (C 14 to C 28 ) were mainly n ‐hexacosanol in Sturmer and n ‐tetracosanol in Dougherty and Granny Smith cultivars, the amounts of these alcohols being, respectively, 53.4, 32.4 and 35.6% of the total alcohols. In all three cultivars the secondary alcohols consisted almost entirely of one component, possibly nonacosan‐10‐ol. The Sturmer waxes were distinguished from those of the Dougherty and Granny Smith by a lower content of linoleic and by a generally higher content of palmitic acid. During storage the amount and composition of the waxes of Sturmers did not change appreciably. The wax content of the Granny Smith cultivar increased up to 268 days and that of the Dougherty up to 70 days of storage. Changes in fatty acid composition also occurred during storage, the most remarkable being the up to 11‐fold elevation of the linolenic acid content of the Granny Smith apples.
ON THE THEORY OF ORDER IN ISAAC WARE'S : A Complete Body of Archtecture (1990)

Isaac Ware ' s ( d1766 ) ACom lete Body of Archite re of 1756 is not only the most important of his works but also one of the remarkable books during the Neo -61assicai perio l in Britain As aresult of tooking it over e present author has drawn his cenclusions as followsWare ' s theQry of the propor ions of orders is not able to be understQod simply in the context of the Re - naissance tradition and he has the different point of view of proportion from bQth at of the Re naissance and that of Perrault ' s and therefore his proposal of the proportions o orders should be regalded as typically English s nce he maintains the plural systems of proportion on the basis of feasibility KeUtvord8
Severe indwelling urinary catheter-associated urethral erosion in four elderly men. (2010)

﻿Medical devices often are overlooked as a potential cause of pressure ulcers. Indwelling urinary catheters have been described as a cause of urethral erosion. In men, the resultant partial-thickness or full-thickness wound can involve a small area of the glans penis or cleave the glans or penile shaft, requiring reconstructive surgery or urinary diversion. During a 3-month period, four elderly men, all residing in one unit of a long-term care facility, were referred to the wound specialist for erosive urethral injuries. All were observed to have a history of improper securement of a rigid style silicone catheter. As part of creating a latex-free environment, the facility had recently replaced the (softer) latex-containing catheters with new silicone catheters. In addition to providing meticulous catheter care and comfort measures for the patients, all securement procedures were reviewed and different silicone catheters were evaluated for their potential to cause pressure ulcers. This case series highlights the importance of careful evaluation of catheter materials and securement devices before selecting them for widespread patient use and emphasizes the need for research focused on catheter composition and pressure injury risk.
Considerations on optical wavelength multiplexing versus optical time multiplexing in transport network (2003)

We compare optical wavelength multiplexing and time multiplexing techniques for optical transport network by studying the space switch sizes of optical cross connects (OXCs) and their interfaces as a function of the fraction of add/drop traffic.
Chemical dehydrohalogenation of halogen-containing polymers (1991)

This review is concerned with the dehydrohalogenation of halogen-containing polymers as a method of obtaining polymers with a system of conjugated multiple bonds. Different dehydrohalogenating agents are described and the mechanism, kinetics and structure of the reaction products are examined. The bibliography includes 159 references.
Nitrate therapy: is there an optimal substance and formulation? (1991)

Nitrate therapy has been shown to be beneficial for the treatment of coronary artery diseases and a number of chemical entities and their respective pharmaceutical formulations are available for clinical use. In this report, the performance of these nitrate drug/formulation combinations is discussed in terms of the relative onset of action, duration of action, tolerance properties/regeneration of reactivity and patient acceptance. A pharmacodynamic action scheme is presented and this allows a systematic assessment of how changes in the nitrate and/or formulation may impact on therapeutic activity. Data suggest that several sustained-release preparations of various nitrates can provide protection against exercise-induced angina for about 12 h on repeated dosing, provided a 'nitrate-free' or 'nitrate-poor' interval is also instituted. The 'ideal' nitrate substance and formulation, which theoretically can provide around-the-clock protection, is not yet available.
Quantum transport with spin dephasing: A nonequlibrium Green’s function approach (2007)

A quantum transport model incorporating spin scattering processes is presented using the nonequilibrium Green's function formalism within the self-consistent Born approximation. This model offers a unified approach by capturing the spin-flip scattering and the quantum effects simultaneously. A numerical implementation of the model is illustrated for magnetic tunnel junction devices with embedded magnetic impurity layers. This model seems to explain three experimentally observed features regarding the dependence of the junction magnetoresistances (JMRs) on the barrier thickness, barrier height, and number of magnetic impurities. It is shown that small variations in magnetic impurity spin states and concentrations could cause large deviations in JMRs.
Tarnish Protection of Silver Using a Hexadecanethiol Self-Assembled Monolayer and Descriptions of Accelerated Tarnish Tests (2001)

A four-step procedure was developed for depositing a hexadecanethiol self-assembled monolayer (SAM) onto the surface of silver in order to provide tarnish resistance. The four steps may be characterized as cleaning, etching, mono-layer self-assembly, and rinsing. A key observation in this work is that an optimal deposition time exists for a given concentration of the hexadecanethiol. For example, a 2 vol% solution (2 mL hexadecanethiol in 98 mL trichloroethylene) required 30 min to 60 min for optimum coating formation. The quality of the coatings was characterized using water drop contact angle measurements and electrochemical impedance spectroscopy (EIS). In addition, two tarnish tests were developed specifically for this project. One test was a lab bench vapor test that could tarnish silver, copper, or brass to a dark color within a few hours. A second test exposed the silver to a stream of a sulfide-containing foam and could tarnish silver to black within several minutes. The degree of tarnishing from these two tests was quantified by measuring the percent reflectance of the surface using visible light.
Mutagenesis via Insertional or Restriction Enzyme-Mediated Integration (REMI) as a Tool to Tag Pathogenicity Related Genes in Plant Pathogenic Fungi (1999)

Random insertional mutagenesis is a powerful tool to investigate the molecular basis of most genetically determined processes, for example in pathogenic fungi. An improved version of this method is the insertional mutagenesis via restriction enzyme mediated integration (REMI). Transformation efficiency and mode of vector integration are species dependent and further influenced by vector conformation, restriction enzyme activity, and transformation protocol. An overview is given, covering the mutants and already identified genes obtained after REMI mutagenesis. An outlook describes the future developments in the field.
A literature review on the application of AI to Identity Access Management (2018)

The main focus of this research is to explore how artificial intelligence may be used in the context of identity and access management. The identity and access management system (IAM) is a prime requisite in the cybersecurity arsenal of many organizations. In addition to mitigating against data breaches, it also helps to manage the risks associated with working remotely and bringing your device – BYOD – into the workplace. Internal data synchronization, customer contact preference management, and fulfilling privacy compliance standards are just a few of the important tasks that IAM is continuously developing to handle in the modern world [1]. It is important to recognize the significance of a well-thought-out and well-developed IAM strategy. Determining who should have accessibility to what information is a tough decision for many companies, and this difficulty makes their information systems insecure. Forrester's study found that 83 percent of companies do not have a mature strategy to identity and access management (IAM). When compared to companies that have implemented their IAM strategy, these companies are twice as likely to have difficulties as a result of a security breach [1]. A clear positive correlation has been found between better IAM methods and decreased security risk, enhanced productivity, greater privileged activity control, and significantly reduced financial loss, according to the study.
Cold Characteristic Development Test of a New SF6 High Voltage Circuit Breaker (2006)

Computer controlled triggering of an impulse generator was implemented in order to perform precisely timed lightning impulse voltage discharges on a new SF <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">6</sub> high voltage circuit breaker while performing a trip operation. Successive discharges at different time intervals would provide an envelope of dielectric withstand and travel characteristic of the specific high voltage circuit breaker. This test not only evaluates the interrupter gap design but also evaluates the gas flow effect in the dynamic dielectric recovery of the interrupter chamber. Gas flow characteristics in the interruption chamber of an SF <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">6</sub> breaker strongly modifies the dielectric withstand recovery rate of any design. Identifying any weakness before power test are performed not only reduces cost and time, but also simplifies design modifications required and provides an insight into the expected performance of the interrupting chamber during actual synthetic power testing. This paper presents the implementation of this testing procedure as well as the results obtained in a new design of a 245 kV, 63 kA SF <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">6</sub> interrupter
IGF‐1 and BDNF promote chick bulbospinal neurite outgrowth in vitro (2005)

Injured neurons in the CNS do not experience significant functional regeneration and so spinal cord insult often results in permanently compromised locomotor ability. The capability of a severed axon to re-grow is thought to depend on numerous factors, one of which is the decreased availability of neurotrophic factors. Application of trophic factors to axotomized neurons has been shown to enhance survival and neurite outgrowth. Although brainstem-spinal connections play a pivotal role in motor dysfunction after spinal cord injury, relatively little is known about the trophic sensitivity of these populations. This study explores the response of bulbospinal populations to various trophic factors. Several growth factors were initially examined for potential trophic effects on the projection neurons of the brainstem. Brain derived neurotrophic factor (BDNF) and insulin-like growth factor (IGF-1) significantly enhance mean process length in both the vestibulospinal neurons and spinal projection neurons from the raphe nuclei. Nerve growth factor (NGF), neurotrophin-4 (NT-4) and glial derived neurotrophic factor (GDNF) did not effect process outgrowth in vestibulospinal neurons. At the developmental stages used in this study, it was determined that receptors for BDNF and IGF-1 were present both on bulbospinal neurons and on surrounding cells with a non-neuronal morphology.
Sequences required for paramutation of the maize b gene map to a region containing the promoter and upstream sequences. (1995)

The b gene encodes a transcriptional regulator of the maize anthocyanin biosynthetic pathway. Certain b alleles participate in paramutation, an allele-specific interaction that heritably alters transcription. The moderately transcribed B' allele heritably reduces the transcription of the highly transcribed B-I allele in a B'/B-I heterozygote, such that the B-I allele becomes B'. To identify the cis-acting sequences required for paramutation, we used B' or B-I alleles to isolate intragenic recombinants with B-Peru, an allele that is insensitive to paramutation and has distinct tissue-specific regulation. Physical mapping of the recombinant alleles showed that most of the crossovers were in a small region near the 5' end of the b-transcribed region. Analysis of the recombinant alleles revealed that the ability to cause and respond to paramutation and the control of tissue-specific expression both localize to the 5' region of the gene. The 3' boundary of these functions lies just upstream of the translation initiation codon. The 5' boundary has been estimated to be no more than 0.1 cM further upstream (1-150 kb). Thus, sequences critical for paramutation lie upstream of the b coding sequences and may include transcriptional regulatory sequences.