gebhart/patrepeval huggingface dataset:
Measurement of plasma B6 vitamer profiles in children with inborn errors of vitamin B6 metabolism using an LC‐MS/MS method (2012)

Vitamin B(6) dependent seizure disorders are an important and treatable cause of childhood epilepsy. The molecular and biochemical basis for some of these disorders has only recently been elucidated and it is likely that inborn errors affecting other parts of this complex metabolic pathway are yet to be described. In man vitamin B(6) ingested from the diet exists as six different vitamers, pyridoxal (PL), pyridoxamine (PM), pyridoxine (PN), pyridoxal 5'-phosphate (PLP), pyridoxamine 5'- phosphate (PMP) and pyridoxine 5'-phosphate (PNP). Its breakdown product, 4-pyridoxic acid (PA), is excreted in urine. Here we describe an analytical LC-MS/MS method to measure all vitameric B(6) forms in plasma and have subsequently applied this methodology to investigate children with vitamin B(6) responsive seizure disorders. We show that patients with inborn errors of B(6) metabolism such as pyridox(am)ine 5'-phosphate oxidase (PNPO) deficiency have characteristic B(6) profiles which allow them to be differentiated from each other and control populations, even when on treatment with B(6). Regardless of diagnosis, patients on treatment doses of pyridoxine hydrochloride and pyridoxal phosphate have markedly elevated levels of some vitameric forms (PLP, PL and PA). Such mega doses of B(6) treatment are known to be associated with neurotoxicity. This LC-MS/MS method will be a useful tool for treatment monitoring and may help further our understanding of mechanisms of neurotoxicity in patient groups.
Dynamic Pressure Transmission Through Agarose Gels (2000)

In biomedical research, agarose gel is widely used in tissue culture systems because it permits growing cells and tissues in a three-dimensional suspension. This is especially important in the application of tissue engineering concepts to cartilage repair because it supports the cartilage phenotype. Mechanical loading, especially compression, plays a fundamental role in the development and repair of cartilage. It would be advantageous to develop a system where cells and tissues could be subjected to compression so that their responses can be studied. There is currently no information on the pressure response of agarose gel when pressure is applied to the gas phase of a culture system. To understand the transmission of pressure through the gel, we set up an apparatus that would mimic an agarose suspension tissue culture system. This consisted of a sealed metal cylinder containing air as well as a layer of agarose submerged in culture medium. Pressure responses were recorded in the air, fluid, gel center, and gel periphery using various frequencies, pressures, gel volumes, and viscosities. Regression analyses show an almost perfect linear relation between gas and gel pressures (r(2) = 0.99987, p < 0.0001, f(x) = 0.9982 x - 0.0286). The pressure transmission was complete and immediate, throughout the range of the applied pressures, frequencies, volumes, and viscosities tested. Applying dynamic pressure to the gas phase results in reproducible pressure in the agarose and, therefore, validates the use of agarose tissue culture systems in studies employing dynamic pressurization in cartilage tissue engineering.
Role of the peri-effect in synthesis and reactivity of highly substituted naphthaldehydes: a novel backbone amide linker for solid-phase synthesis (2004)

Handles (linkers) with an aldehyde functionality that permits the anchoring of substrates by reductive amination have, since their first report in the mid-1990s, become widely-used tools in solid-phase synthesis. In the synthesis of peptides, they allow anchoring of the growing peptide chain through a backbone amide, thus giving easy access to C-terminal modified or cyclic peptides. Recently, we described two new handles (NAL-1 and NAL-2) with dialkoxynaphthaldehyde core structures. Here, we describe the design, synthesis and properties of a novel trialkoxynaphthalene-based backbone amide linker (NAL-3). The NAL-3 handle is based on a trialkoxynaphthaldehyde (NALdehyde-3) that was synthesized in nine high-yielding steps from 3-methoxyphenylacetic acid in 51% overall yield. The naphthalene ring system was constructed using a regioselective methanesulfonic acid-catalyzed ring-closing reaction. The tetra-substituted naphthalene derivative 1,3,6-trimethoxynaphthalene-2-carbaldehyde (7) was selectively demethylated in the 1 position using BBr(3). The selectivity of this reaction is discussed, based on the crystal structures of reactant and product, 1-hydroxy-3,6-dimethoxy-naphthalene-2-carbaldehyde (8), and in the context of the peri-effect. The new handle was anchored to an aminomethylated poly(styrene) solid support, followed by assembly of a model dipeptide, then a study of the cleavage properties under acidic conditions was carried out. Surprisingly, the trialkoxynaphthaldehyde-based handle proved less acid-labile than the dialkoxynaphthaldehyde handles, and this fact is discussed with respect to handle design.
Stereospecific conversion of peptides into .beta.-lactams (1975)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTStereospecific conversion of peptides into .beta.-lactamsJack E. Baldwin, Andrew Au, Michael Christie, Stephen B. Haber, and David HessonCite this: J. Am. Chem. Soc. 1975, 97, 20, 5957–5958Publication Date (Print):October 1, 1975Publication History Published online1 May 2002Published inissue 1 October 1975https://pubs.acs.org/doi/10.1021/ja00853a075https://doi.org/10.1021/ja00853a075research-articleACS PublicationsRequest reuse permissionsArticle Views142Altmetric-Citations45LEARN 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 InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
THE DEVELOPMENT OF SHORT BOWL ULTRACENTRIFUGES. Progress ReporT (1959)

Progress is reponted on lifetime tests of rotors and determination of power loss of the scoop system. (T.R.H.)
Investigation of Trypanothione Reductase as a Drug Target in Trypanosoma brucei (2009)

There is an urgent need for new drugs for the treatment of tropical parasitic diseases such as human African trypanosomiasis, which is caused by Trypanosoma brucei. The enzyme trypanothione reductase (TryR) is a potential drug target within these organisms. Herein we report the screening of a 62,000 compound library against T. brucei TryR. Further work was undertaken to optimise potency and selectivity of two novel-compound series arising from the enzymatic and whole parasite screens and mammalian cell counterscreens. Both of these series, containing either a quinoline or pyrimidinopyrazine scaffold, yielded low micromolar inhibitors of the enzyme and growth of the parasite. The challenges of inhibiting TryR with druglike molecules is discussed.
Antisite effect on hole-mediated ferromagnetism in (Ga,Mn)As (2006)

We study the Curie temperature and hole density of (Ga,Mn)As while systematically varying the As-antisite density. Hole compensation by As-antisites limits the Curie temperature and can completely quench long-range ferromagnetic order in the low doping regime of 1%--2% Mn. Samples are grown by molecular beam epitaxy without substrate rotation in order to smoothly vary the As to Ga flux ratio across a single wafer. This technique allows for a systematic study of the effect of As stoichiometry on the structural, electronic, and magnetic properties of (Ga,Mn)As. For concentrations less than 1.5% Mn, a strong deviation from ${T}_{C}\ensuremath{\propto}{p}^{0.33}$ is observed. Our results emphasize that proper control of As-antisite compensation is critical for controlling the Curie temperatures in (Ga,Mn)As at the low doping limit.
Dancing with uncertainty (2012)

We present Dubstep, a novel system that uses the find-transform-navigate paradigm to automatically explore new parallelization opportunities in already parallelized (fully-synchronized) programs by opportunistically relaxing synchronization primitives. This set of transformations generates a space of alternative, possibly non-deterministic, parallel programs with varying performance and accuracy characteristics. The freedom to generate parallel programs whose output may differ (within statistical accuracy bounds) from the output of the original program enables a significantly larger optimization space. Dubstep then searches this space to find a parallel program that will, with high likelihood, produce outputs that are acceptably close to the outputs that the original, fully synchronized parallel program would have produced.
Multiple Myeloma Treatment in Real-world Clinical Practice: Results of a Prospective, Multinational, Noninterventional Study (2018)

The results of our prospective study have revealed great diversity in the treatment regimens used to manage MM in real-life practice. This diversity was linked to factors such as novel agent accessibility and evolving treatment recommendations. Our results provide insight into associated clinical benefits.
Initial Experience With Larger Laser Sheaths for the Removal of Transvenous Pacemaker and Implantable Defibrillator Leads (1999)

The 14F and 16F laser sheaths offer an extraction option for larger long-term transvenous pacemaker and defibrillator leads that is as safe and effective as the 12F laser sheath.
Adult murine cardiomyocytes exhibit regenerative activity with cell cycle reentry through STAT3 in the healing process of myocarditis (2017)

Mammalian cardiomyocytes substantially lose proliferative capacity immediately after birth, limiting adult heart regeneration after injury. However, clinical myocarditis appears to be self-limiting with tissue-reparative properties. Here, we investigated the molecular mechanisms underlying the recovery from myocarditis with regard to cardiomyocyte proliferation using an experimental autoimmune myocarditis (EAM) model. Three weeks after EAM induction (EAM3w), cardiac tissue displayed infiltration of inflammatory cells with cardiomyocyte apoptosis. However, by EAM5w, the myocardial damage was remarkably attenuated, associated with an increase in cardiomyocytes that were positively stained with cell cycle markers at EAM3w. Cardiomyocyte fate mapping study revealed that the proliferating cardiomyocytes primarily derived from pre-existing cardiomyocytes. Signal transducer and activator of transcription 3 (STAT3) was robustly activated in cardiomyocytes during inflammation, accompanied by induction of interleukin-6 family cytokines. Cardiomyocyte-specific ablation of STAT3 gene suppressed the frequency of cycling cardiomyocytes in the recovery period without influencing inflammatory status, resulting in impaired tissue repair and cardiac dysfunction. Finally, microarray analysis revealed that the expression of regeneration-related genes, metallothioneins and clusterin, in cardiomyocytes was decreased by STAT3 gene deletion. These data show that adult mammalian cardiomyocytes restore regenerative capacity with cell cycle reentry through STAT3 as the heart recovers from myocarditis-induced cardiac damage.
Single Crystal Metals Encapsulated in Carbon Nanoparticles (1993)

Single-domain microcrystals of LaC 2 encapsulated within nanoscale polyhedral carbon particles have been synthesized in a carbon arc. Typical particle sizes are on the order of 20 to 40 nanometers. The stoichiometry and phase of the La-containing crystals have been assigned from characteristic lattice spacings observed by high-resolution transmission electron microscopy and energy dispersive spectroscopy (EDS). EDS spectra show that La and C are the only elements present. Characteristic interatomic distances of 3.39 and 2.78 angstroms identify the compound inside the nanoparticle cavities as α-LaC 2 , the phase of LaC 2 that is stable at room temperature. Bulk α-LaC 2 is metallic and hydrolytic. Observation of crystals of pure encapsulated α-LaC 2 that were exposed to air for several days before analysis indicates that the LaC 2 is protected from degradation by the carbon polyhedral shells of the nanoparticles. A high percentage of the carbon nanoparticles have encapsulated LaC 2 single crystals. These carbon-coated metal crystals form a new class of materials that can be protected in their pure or carbide forms and may have interesting and useful properties.
4-(4-Iodoanilino)-2-methylene-4-oxobutanoic acid (2012)

In the title compound, C11H10INO3, an addition product of itaconic acid anhydride and 4-iodo-aniline, the least-squares planes defined by the atoms of the aromatic moiety and the non-H atoms of the carb-oxy-lic acid group enclose an angle of 74.82 (11)°. In the crystal, classical O-H⋯O hydrogen bonds formed by carb-oxy-lic groups, as well as N-H⋯O hydrogen bonds formed by amide groups, are present along with C-H⋯O contacts. Together, these connect the mol-ecules into dimeric chains along the b-axis direction.
Novel Contribution of Secreted Amyloid-β Precursor Protein to White Matter Brain Enlargement in Autism Spectrum Disorder (2019)

The most replicated neuroanatomical finding in autism is the tendency toward brain overgrowth, especially in younger children. Research shows that both gray and white matter are enlarged. Proposed mechanisms underlying brain enlargement include abnormal inflammatory and neurotrophic signals that lead to excessive, aberrant dendritic connectivity via disrupted pruning and cell adhesion, and enlargement of white matter due to excessive gliogenesis and increased myelination. Amyloid-β protein precursor (βAPP) and its metabolites, more commonly associated with Alzheimer's disease (AD), are also dysregulated in autism plasma and brain tissue samples. This review highlights findings that demonstrate how one βAPP metabolite, secreted APPα, and the ADAM family α-secretases, may lead to increased brain matter, with emphasis on increased white matter as seen in autism. sAPPα and the ADAM family α-secretases contribute to the anabolic, non-amyloidogenic pathway, which is in contrast to the amyloid (catabolic) pathway known to contribute to Alzheimer disease. The non-amyloidogenic pathway could produce brain enlargement via genetic mechanisms affecting mRNA translation and polygenic factors that converge on molecular pathways (mitogen-activated protein kinase/MAPK and mechanistic target of rapamycin/mTOR), promoting neuroinflammation. A novel mechanism linking the non-amyloidogenic pathway to white matter enlargement is proposed: α-secretase and/or sAPPα, activated by ERK receptor signaling activates P13K/AKt/mTOR and then Rho GTPases favoring myelination via oligodendrocyte progenitor cell (OPC) activation of cofilin. Applying known pathways in AD to autism should allow further understanding and provide options for new drug targets.
Comparison of Myocardial Infarction with Sequential Ligation of the Left Anterior Descending Artery and Its Diagonal Branch in Dogs and Sheep (2003)

We report a comparison of the effects of myocardial infarction in dogs and sheep using sequential ligation of the left anterior descending artery (LAD) and its diagonal branch (DA), with hemodynamic, ultrasonographic and pathological evaluations. Five animals were used in each group. After surgical preparation, the LAD was ligated at a point approximately 40% of the distance from the apex to the base of the heart, and after one hour, the DA was ligated at the same level. Hemodynamic and ultrasonographic measurements were performed preligation, 30 minutes after LAD ligation, and 1 hour after DA ligation. As a control, two animals in each group were used for the simultaneous ligation of the LAD and the DA. Two months after the coronary ligation, the animals were evaluated as previously, and killed for postmortem examination of their hearts. All seven animals in the dog group survived the experimental procedures, while in the sheep group only animals with sequential ligation of the LAD and DA survived. Statistically significant decreases in systemic arterial blood pressure and cardiac output, and an increase in the pulmonary artery capillary wedge pressure (PACWP) were observed one hour after sequential ligation of the LAD and its DA in the sheep, while only systemic arterial pressures decreased in the dog. Ultrasonographic analyses demonstrated variable degrees of anteroseptal dyskinesia and akinesia in all sheep, but in no dogs. Data two months after coronary artery ligation showed significant increases in central venous pressure, pulmonary artery pressure, and PACWP in the sheep, but not in the dog. Left ventricular end-diastolic dimension and left ventricular end-systolic dimension in ultrasonographic studies were also increased only in the sheep. Pathologically, the well-demarcated thin-walled transmural anteroseptal infarcts with chamber enlargement were clearly seen in all specimens of sheep, and only-mild-to-moderate chamber enlargements with endocardial fibrosis were observed in the dog hearts. In conclusion, this study confirms that the dog is not a suitable model for myocardial infarction with failure by coronary artery ligation despite negligent operative mortality, when compared directly with an ovine model.
Finding melanoma drugs through a probabilistic knowledge graph (2016)

Metastatic cutaneous melanoma is an aggressive skin cancer with some progression-slowing treatments but no known cure. The omics data explosion has created many possible drug candidates, however filtering criteria remain challenging, and systems biology approaches have become fragmented with many disconnected databases. Using drug, protein, and disease interactions, we built an evidence-weighted knowledge graph of integrated interactions. Our knowledge graph-based system, ReDrugS, can be used via an API or web interface, and has generated 25 high quality melanoma drug candidates. We show that probabilistic analysis of systems biology graphs increases drug candidate quality compared to non-probabilistic methods. Four of the 25 candidates are novel therapies, three of which have been tested with other cancers. All other candidates have current or completed clinical trials, or have been studied in in vivo or in vitro . This approach can be used to identify candidate therapies for use in research or personalized medicine.
New Aspects in the Treatment of Parkinson's Disease (2003)

In den letzten Jahrzehnten hat das Verständnis der Pathobiologie der Parkinson-Erkrankung in der Neurologie erheblich zugenommen. Diese neuen Erkenntnisse spiegeln sich in den Neuentwicklungen verschiedenster Pharmaka wider. Neben den verschiedenen Formen der L-Dopa-Administration, den verschiedenen Dopaminagonisten, der MAO-B-Hemmung oder der COMT-Hemmung spielen nicht-dopaminerge Strategien zunehmend eine besondere Rolle. Ein großes Interesse bezieht sich auf die potenziell neuroprotektiven Wirkungen bereits erhältlicher Pharmaka, aber auch auf die Entwicklung neuer Pharmaka mit anti-glutamaterger, anti-apoptotischer und antioxidativer Wirkung.
Evaluating Brightness Temperature Information for Estimating Microwave Land Surface and Vegetation Properties (2019)

Remote sensing of geophysical parameters often requires parameter estimation from mutually dependent measurements, reducing retrieval robustness when the number of retrieved parameters equals the number of unknowns. The actual number of parameters that can be retrieved from the total information (e.g., degrees of information (DOI)) is reviewed here in the context of current L-band (1.4 GHz) satellite measurements for retrieving soil and vegetation water content. A limitation of DOI metric is noted where measurements at the noise floor (i.e., in vegetated regions) tend to spuriously decrease estimated mutual information. Thus, the signal-to-noise ratio must be considered together with DOI. A proposed retrieval technique that overcomes the mutually-dependent information, called the multi-temporal dual-channel algorithm, is reviewed and its microwave vegetation parameter retrievals are discussed.
The Pseudomonas aeruginosa Wsp pathway undergoes positive evolutionary selection during chronic infection (2018)

Pathogens experience pressure in an infection to adapt, with selection favoring mutants that persist. Pseudomonas aeruginosa commonly adapts by evolving mutants with hyper-biofilm production that evade clearance. Despite our understanding of the adaptive phenotypes, studying their emergence and dynamics in an infection has proven challenging. Here we used a porcine full-thickness burn wound model of chronic infection to study how mixed strains of P. aeruginosa adaptively evolve. Wounds were infected with six P. aeruginosa strains, including the model PA14 strain (PA14-1), and biopsies taken at 3, 14, and 28 days post-infection. Rugose small-colony variants (RSCVs) were detected at 3-d and persisted, with the majority evolved from PA14-1. Whole genome sequencing of PA14-1 RSCVs revealed driver mutations exclusively in the wsp pathway. RSCVs also acquired CRISPR-Cas adaptive immunity to prophages isolated from the P. aeruginosa wound isolate (B23-2) present in the inoculum. The rapid rise of RSCVs to detectable frequencies is evidence of positive selection of the Wsp chemosensory system and suggests that RSCVs may arise earlier in an infection than originally appreciated, to facilitate infection. Given the prevalence of RSCVs in chronic infections, we predict that RSCVs may be a common, early adaptation during infections.
Rotational manipulation of single cells and organisms using acoustic waves (2016)

The precise rotational manipulation of single cells or organisms is invaluable to many applications in biology, chemistry, physics and medicine. In this article, we describe an acoustic-based, on-chip manipulation method that can rotate single microparticles, cells and organisms. To achieve this, we trapped microbubbles within predefined sidewall microcavities inside a microchannel. In an acoustic field, trapped microbubbles were driven into oscillatory motion generating steady microvortices which were utilized to precisely rotate colloids, cells and entire organisms (that is, C. elegans). We have tested the capabilities of our method by analysing reproductive system pathologies and nervous system morphology in C. elegans. Using our device, we revealed the underlying abnormal cell fusion causing defective vulval morphology in mutant worms. Our acoustofluidic rotational manipulation (ARM) technique is an easy-to-use, compact, and biocompatible method, permitting rotation regardless of optical, magnetic or electrical properties of the sample under investigation.