gebhart/patrepeval huggingface dataset:
A genetic mouse model for progressive ablation and regeneration of insulin producing beta-cells (2014)

The putative induction of adult β-cell regeneration represents a promising approach for the treatment of type 1 diabetes. Toward this ultimate goal, it is essential to develop an inducible model mimicking the long-lasting disease progression. In the current study, we have established a novel β-cell ablation mouse model, in which the β-cell mass progressively declines, as seen in type 1 diabetes. The model is based on the β-cell specific genetic ablation of the transcription initiation factor 1A, TIF-IA, essential for RNA Polymerase I activity (TIF-IA(Δ/Δ)). Using this approach, we induced a slow apoptotic response that eventually leads to a protracted β-cell death. In this model, we observed β-cell regeneration that resulted in a complete recovery of the β-cell mass and normoglycemia. In addition, we showed that adaptive proliferation of remaining β-cells is the prominent mechanism acting to compensate for the massive β-cell loss in young but also aged mice. Interestingly, at any age, we also detected β-like cells expressing the glucagon hormone, suggesting a transition between α- and β-cell identities or vice versa. Taken together, the TIF-IA(Δ/Δ) mouse model can be used to investigate the potential therapeutic approaches for type 1 diabetes targeting β-cell regeneration.
Nucleotide Analogue Prodrug Tenofovir Disoproxil Enhances Lymphoid Cell Loading following Oral Administration in Monkeys (2009)

The antiviral drug tenofovir (TFV) is orally administered as the fumarate salt of its disoproxil prodrug (TFV disoproxil fumarate (TDF)). TFV is a dianion at physiological pH and, as a result, has poor lipid membrane permeability. Administration of the lipophilic and cell-permeable prodrug, TFV disoproxil, enhances the oral absorption of TFV. In order to determine whether oral administration of TDF also increases distribution to sites of viral infection, the plasma and circulating lymphoid cell pharmacokinetics of TFV and its phosphorylated metabolites were assessed following a single oral TDF or subcutaneous TFV administration at doses yielding equivalent plasma exposures to TFV in macaques. Despite TFV disoproxil's lack of plasma stability and undetectable levels in the first plasma samples taken, oral administration of TDF resulted in 7.9-fold higher peripheral blood mononuclear cell exposures to the active metabolite, TFV-diphosphate. The apparent plasma terminal half-life (t(1/2)) of TFV was also longer following oral TDF relative to subcutaneous TFV administration (median t(1/2) of 15.3 and 3.9 h, respectively), suggesting broader distribution to cells and tissues outside of the central plasma compartment. In conclusion, the disoproxil pro-moiety enhances not only the oral absorption of TFV but also tissue and lymphoid cell loading. These results illustrate that administration of even a fleeting prodrug can increase target tissue loading and give valuable insight for future prodrug development.
Re: Klinefelter Syndrome: How, What, and Why? (2012)

No AccessJournal of UrologyAdult Urology1 Feb 2013Re: Klinefelter Syndrome: How, What, and Why? Craig NiederbergerM.D. Craig NiederbergerCraig Niederberger More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2012.10.102AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail "Re: Klinefelter Syndrome: How, What, and Why?." The Journal of Urology, 189(2), p. 657 © 2013 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 189Issue 2February 2013Page: 657 Advertisement Copyright & Permissions© 2013 by American Urological Association Education and Research, Inc.MetricsAuthor Information Craig Niederberger More articles by this author Expand All Advertisement Loading ...
Causal meets Submodular: Subset Selection with Directed Information (2016)

We study causal subset selection with Directed Information as the measure of prediction causality. Two typical tasks, causal sensor placement and covariate selection, are correspondingly formulated into cardinality constrained directed information maximizations. To attack the NP-hard problems, we show that the first problem is submodular while not necessarily monotonic. And the second one is ``nearly'' submodular. To substantiate the idea of approximate submodularity, we introduce a novel quantity, namely submodularity index (SmI), for general set functions. Moreover, we show that based on SmI, greedy algorithm has performance guarantee for the maximization of possibly non-monotonic and non-submodular functions, justifying its usage for a much broader class of problems. We evaluate the theoretical results with several case studies, and also illustrate the application of the subset selection to causal structure learning.
Houttuynia cordata Thunb Fraction Induces Human Leukemic Molt-4 Cell Apoptosis through the Endoplasmic Reticulum Stress Pathway (2012)

Houttuynia cordata Thunb (HCT) is a native herb found in Southeast Asia which features various pharmacological activities against allergy, inflammation, viral and bacterial infection, and cancer. The aims of this study were to determine the cytotoxic effect of 6 fractions obtained from silica gel column chromatography of alcoholic HCT extract on human leukemic Molt-4 cells and demonstrate mechanisms of cell death. Six HCT fractions were cytotoxic to human lymphoblastic leukemic Molt-4 cells in a dose-dependent manner by MTT assay, fraction 4 exerting the greatest effects. Treatment with IC50 of HCT fraction 4 significantly induced Molt-4 apoptosis detected by annexinV-FITC/propidium iodide for externalization of phosphatidylserine to the outer layer of cell membrane. The mitochondrial transmembrane potential was reduced in HCT fraction 4-treated Molt-4 cells. Moreover, decreased expression of Bcl-xl and increased levels of Smac/Diablo, Bax and GRP78 proteins were noted on immunoblotting. In conclusion, HCT fraction 4 induces Molt-4 apoptosis cell through an endoplasmic reticulum stress pathway.
Plasma‐Assisted Atomic Layer Deposition of PtO<sub><i>x</i></sub> from (MeCp)PtMe<sub>3</sub> and O<sub>2</sub> Plasma (2014)

Abstract Atomic layer deposition (ALD) using (MeCp)PtMe 3 and O 2 gas or O 2 plasma is a well‐established technique for the deposition of thin films of Pt, but the potential of ALD to deposit platinum oxide (PtO x ) has not yet been systematically explored. This work demonstrates how PtO x can be deposited by plasma‐assisted (PA)‐ALD in a temperature window from room temperature (RT) to 300 °C by controlling the O 2 plasma and (MeCp)PtMe 3 exposure. With increasing substrate temperature, the thermal stability of PtO x decreases and the reducing activity of the precursor ligands increases. Therefore, longer O 2 plasma exposures and/or lower (MeCp)PtMe 3 exposures are required to obtain PtO x at higher temperatures. Furthermore, it is established that, during the nucleation stage, PtO x ALD starts by the formation of islands that grow and coalesce during the initial ∼40 cycles. Closed‐layer thin films of PtO x with an O/Pt ratio of 2.5 can be deposited at 100 °C with a minimal thickness of only ∼2 nm. It is also demonstrated that a conformality of ∼90% can be reached for PtO x films in trenches with an aspect ratio of 9 when using optimized O 2 plasma and precursor exposure times.
Incidence of dengue fever in an urban slum community in Salvador, Brazil (2012)

Introduction: Symptoms of dengue infection are nonspecific, complicating diagnosis and case reporting. Active surveillance is needed to better characterize disease burden. The objectives of this study were to estimate the incidence and identify risk factors for dengue fever (DF) in an urban slum community in Salvador, Brazil.
Automatic inference model construction for computer-aided diagnosis of lung nodule: Explanation adequacy, inference accuracy, and experts’ knowledge (2018)

We aimed to describe the development of an inference model for computer-aided diagnosis of lung nodules that could provide valid reasoning for any inferences, thereby improving the interpretability and performance of the system. An automatic construction method was used that considered explanation adequacy and inference accuracy. In addition, we evaluated the usefulness of prior experts' (radiologists') knowledge while constructing the models. In total, 179 patients with lung nodules were included and divided into 79 and 100 cases for training and test data, respectively. F-measure and accuracy were used to assess explanation adequacy and inference accuracy, respectively. For F-measure, reasons were defined as proper subsets of Evidence that had a strong influence on the inference result. The inference models were automatically constructed using the Bayesian network and Markov chain Monte Carlo methods, selecting only those models that met the predefined criteria. During model constructions, we examined the effect of including radiologist's knowledge in the initial Bayesian network models. Performance of the best models in terms of F-measure, accuracy, and evaluation metric were as follows: 0.411, 72.0%, and 0.566, respectively, with prior knowledge, and 0.274, 65.0%, and 0.462, respectively, without prior knowledge. The best models with prior knowledge were then subjectively and independently evaluated by two radiologists using a 5-point scale, with 5, 3, and 1 representing beneficial, appropriate, and detrimental, respectively. The average scores by the two radiologists were 3.97 and 3.76 for the test data, indicating that the proposed computer-aided diagnosis system was acceptable to them. In conclusion, the proposed method incorporating radiologists' knowledge could help in eliminating radiologists' distrust of computer-aided diagnosis and improving its performance.
Electronic structure of organometallic compounds. 18. Electronic structure of bis(pentadienyl)iron. Semiempirical calculations and photoelectron spectra (1982)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTElectronic structure of organometallic compounds. 18. Electronic structure of bis(pentadienyl)iron. Semiempirical calculations and photoelectron spectraMichael C. Boehm, Mirjana Eckert-Maksic, Richard D. Ernst, David R. Wilson, and Rolf GleiterCite this: J. Am. Chem. Soc. 1982, 104, 10, 2699–2707Publication Date (Print):May 1, 1982Publication History Published online1 May 2002Published inissue 1 May 1982https://doi.org/10.1021/ja00374a004RIGHTS & PERMISSIONSArticle Views75Altmetric-Citations34LEARN 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 (995 KB) Get e-Alerts Get e-Alerts
Functional Effects of Different Medium-Chain Acyl-CoA Dehydrogenase Genotypes and Identification of Asymptomatic Variants (2012)

Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency (OMIM 201450) is the most common inherited disorder of fatty acid metabolism presenting with hypoglycaemia, hepatopathy and Reye-like symptoms during catabolism. In the past, the majority of patients carried the prevalent c.985A>G mutation in the ACADM gene. Since the introduction of newborn screening many other mutations with unknown clinical relevance have been identified in asymptomatic newborns. In order to identify functional effects of these mutant genotypes we correlated residual MCAD (OMIM 607008) activities as measured by octanoyl-CoA oxidation in lymphocytes with both genotype and relevant medical reports in 65 newborns harbouring mutant alleles. We identified true disease-causing mutations with residual activities of 0 to 20%. In individuals carrying the c.199T>C or c.127G>A mutation on one allele, residual activities were much higher and in the range of heterozygotes (31%-60%). Therefore, both mutations cannot clearly be associated with a clinical phenotype. This demonstrates a correlation between the octanoyl-CoA oxidation rate in lymphocytes and the clinical outcome. With newborn screening, the natural course of disease is difficult to assess. The octanoyl-CoA oxidation rate, therefore, allows a risk assessment at birth and the identification of new ACADM genotypes associated with asymptomatic disease variants.
Flying DNA Cation Radicals in the Gas Phase: Generation and Action Spectroscopy of Canonical and Noncanonical Nucleobase Forms (2021)

Gas-phase chemistry of cation radicals related to ionized nucleic acids has enjoyed significant recent progress thanks to the development of new methods for cation radical generation, ion spectroscopy, and reactivity studies. Oxidative methods based on intramolecular electron transfer in transition-metal complexes have been used to generate nucleobase and nucleoside cation radicals. Reductive methods relying on intermolecular electron transfer in gas-phase ion-ion reactions have been utilized to generate a number of di- and tetranucleotide cation radicals, as well as charge-tagged nucleoside radicals. The generated cation radicals have been studied by infrared and UV-visible action spectroscopy and ab initio and density functional theory calculations, providing optimized structures, harmonic frequencies, and excited-state analysis. This has led to the discovery of stable noncanonical nucleobase cation radicals of unusual electronic properties and extremely low ion-electron recombination energies. Intramolecular proton-transfer reactions in cation radical oligonucleotides and Watson-Crick nucleoside pairs have been studied experimentally, and their mechanisms have been elucidated by theory. Whereas the range of applications of the oxidative methods is currently limited to nucleobases and readily oxidizable guanosine, the reductive methods can be scaled up to generate large oligonucleotide cation radicals including double-strand DNA. Challenges in the experimental and computational approach to DNA cation radicals are discussed.
The Solution Structure of the Complex Formed between α-Bungarotoxin and an 18-mer Cognate Peptide Derived from the α1 Subunit of the Nicotinic Acetylcholine Receptor from Torpedo californica (2001)

The region encompassing residues 181-98 on the 1 subunit of the muscle-type nicotinic acetylcholine receptor forms a major determinant for the binding of -neurotoxins. We have prepared an 15 N-enriched 18- amino acid peptide corresponding to the sequence in this region to facilitate structural elucidation by multidimensional NMR. Our aim was to determine the structural basis for the high affinity, stoichiometric complex formed between this cognate peptide and -bungarotoxin, a long -neurotoxin. Resonances in the complex were assigned through heteronuclear and homonuclear NMR experiments, and the resulting interproton distance constraints were used to generate ensemble structures of the complex. Thr 8 , Pro 10 , Lys 38 , Val 39 , Val 40 , and Pro 69 in -bungarotoxin and Tyr 189 , Tyr 190 , Thr 191 , Cys 192 , Asp 195 , and Thr 196 in the peptide participate in major intermolecular contacts. A comparison of the free and bound -bungarotoxin structures reveals significant conformational rearrangements in flexible regions of -bungarotoxin, mainly loops I, II, and the C-terminal tail. Furthermore, several of the calculated structures suggest that cation-interactions may be involved in binding. The root mean square deviation of the polypeptide backbone in the complex is 2.07 . This structure provides, to date, the highest resolution description of the contacts between a prototypic -neurotoxin and its cognate recognition sequence.
Solvent-sample interactions in thermospray mass spectrometry of antineoplastic nitrogen mustards (1989)

Conditions are reported for the optimization of thermospray mass spectrometric analysis of antineoplastic nitrogen mustard alkylating agents. In aqueous ammonium acetate mobile phase, multiple sequential solvolytic reactions occur with these highly labile compounds, and protonated molecular ions of the reaction products are observed. However, when high proportions of acetonitrile or other organic modifier are added to the mobile phase, solvolytic reactions are much reduced and abundant protonated molecular ions are detected. One exception to these observations is phosphoramide mustard, which solvolyses under all conditions attempted. A lower limit for detection of melphalan using direct injection and summing the ion current between m/z 120 and 870 is about 150 ng. Successful thermospray liquid chromatography/mass spectrometry of these compounds should be possible using high percentages of methanol in the mobile phase or increasing the organic content by post-column solvent modification.
A Study on Relationship Between Period and Number of Divisions in Piecewise Logistic Map over Integers (2021)

The piecewise logistic map proposed by Wang, Liu and Lei provided a wider range of the control parameter than one by the logistic map. However, it is not clear enough to describe relations between the number of divisions and properties of the map. In this paper, we investigate how the period and link length change with respect to number of divisions. As a result, we confirmed period and link length increases or decreases periodically. Further, we confirmed randomness of long period sequence comparable to the randomness of logistic map over integers with high available bits for 2 bits.
EVALUATING THE IMPORTANCE OF DROP SIZE AND SPREADING ANGLE IN NEAR-FIELD SPRAY CALCULATIONS (2020)

Predicting drop size has remained an important aspect in the development of Lagrangian-Eulerian (LE) and other spray models. In the present work, the importance of drop size and spreading angle are evaluated by employing high-fidelity atomization simulations using an algebraic volume of fluid (VoF) approach (InterFoam). The process begins by extracting an axial drop size profile (D32VoF) from VoF results and imposing this profile directly on LE calculations, thereby excluding all breakup models and isolating the effect of the LE calculations on the accuracy of the spray predictions. This LE accuracy is evaluated based on comparisons to projected mass density maps generated by the VoF calculations. The results show that, even with the imposition of the D32VoF profile, the LE calculations exhibit significant errors in comparison to VoF results. This discrepancy emphasizes that having the correct breakup model in LE computations can still lead to significant errors. Additionally, the spreading angle is found to play a much more important role in the prediction of spray mass distribution in comparison to drop size. A key ingredient missing in LE calculations, which is mostly responsible for the errors observed, is the ability of the LE spray model to replicate the axially developing spreading angle, which we believe is partially based on the complex momentum transfer between the gas phase and a large population of dynamically evolving and highly nonspherical liquid elements.
Operational Benefits of Designing Acid-Soluble Drilling Fluids for Horizontal Wells in HTHP Conditions (2016)

Abstract Issues associated with stuck pipe result in huge losses in the world oil industry. Historically, horizontal wells drilled in Saudi Arabia have been known to present severe stuck-pipe challenges. Thus to mitigate the problems arising due to stuck-pipe issues, a new drilling fluid has been designed which employs a combination of two different weighting agents viz. barite and manganese tetroxide (Mn3O4). The use of such a combination as a weighting material in a drilling fluid provides both operational and monetary benefits. Manganese tetroxide is spherical in nature and has a small particle size (D50=1 µm) as compared to barite (D50=20 µm) Moreover, Mn3O4 also has a higher specific gravity (4.95 g/cm3) as compared to barite (SG= 4.20 and). This high specific gravity of manganese tetroxide makes it a good weighting material to reduce solids loading and settling in drilling fluids as compared to the conventionally used barite. Another advantage of Mn3O4 is that it is acid-soluble. This acid solubility of Mn3O4 provides more operational benefits when a fluid with a combination of barite and Mn3O4 is used as weighting agent. The acid solubility of Mn3O4 makes the use of acids or acid precursors possible in partially dissolving Mn3O4-barite based filter-cakes. This partial breakage of the filter cake is expected to free the pipe thereby mitigating the problems associated with stuck pipe incidents. Another benefit of using a combination of barite and Mn3O4 would involve reduced fluid cost as compared to a fluid formulated with Mn3O4 alone as the weighting agent. Thus, this paper presents a solution in mitigating stuck pipe issues and showcases the benefits of using such a combination of barite and manganese tetroxide as weighting materials in 100pcf, 120pcf and 150pcf drilling fluids hot rolled at 270°F /250°F/300°F respectively. The experimental work in this paper involves measuring rheological properties, HTHP filtration and static sagging resistance of the fluid at the specified temperature. The paper also describes the results of using different organic acid based filter-cake breaker fluids for the partial dissolution of manganese tetroxide based filter cake. Comparative studies of fluids formulated with 100% barite and a blend of manganese tetroxide and barite show that fluids formulated with a combination of barite and Mn3O4 provides increased sag resistance as compared to a drilling fluid formulated with barite alone as the weighting agent.
Perspective on “The Role of Mg17Al12 Phase in the Corrosion of Mg Alloy AZ91,” by O. Lunder, J.E. Lein, T.Kr. Aune, and K. Nisancioglu, <i>Corrosion</i> 45, 9 (1989): p. 741-748 (2019)

Abstract: The corrosion of magnesium has remained a significant engineering (and scientific) challenge for close to a century. In the context of magnesium alloys, the alloy microstructure (from the nanoscale to the millimeter scale) plays a key role in influencing the alloy corrosion rate and morphology. The pioneering work that coupled quantitative and analytical microstructural analysis, with the attendant corrosion response, set the benchmark for the field of corrosion metallurgy that followed. This perspective provides a brief context and background for describing the relevance and impact of the classic article.