gebhart/patrepeval huggingface dataset:
Intestinal bicarbonate secretion in cystic fibrosis mice. (2001)

Gene-targeted disruption of the cystic fibrosis transmembrane conductance regulator (CFTR) in mice results in an intestinal disease phenotype that is remarkably similar to bowel disease in cystic fibrosis patients. In the intestinal segment downstream from the stomach (i.e., the duodenum), CFTR plays an important role in bicarbonate secretion that protects the epithelium from acidic gastric effluent. In this report, we examine the role of CFTR in cAMP-stimulated bicarbonate secretion in the murine duodenum and the mechanisms of acid-base transport that are revealed in CFTR knockout (CF) mice. Ion substitution, channel blocker and pH stat studies comparing duodena from wild-type and CF mice indicate that CFTR mediates a HCO(3)(-) conductance across the apical membrane of the epithelium. In the presence of a favorable cell-to-lumen HCO(3)(-) gradient, the CFTR-mediated HCO(3)(-) current accounts for about 80% of stimulated HCO(3)(-) secretion. Exposure of the duodenal mucosa to acidic pH reveals another role of CFTR in facilitating HCO(3)(-) secretion via an electroneutral, 4,4'-diisothiocyanato-stilbene-2,2' disulfonic acid (DIDS) sensitive Cl(-)/HCO(3)(-) exchange process. In CF duodenum, other apical membrane acid-base transporters retain function, thereby affording limited control of transepithelial pH. Activity of a Cl(-)-dependent anion exchanger provides near-constant HCO(3)(-) secretion in CF intestine, but under basal conditions the magnitude of secretion is lessened by simultaneous activity of a Na(+)/H(+) exchanger (NHE). During cAMP stimulation of CF duodenum, a small increase in net base secretion is measured but the change results from cAMP inhibition of NHE activity rather than increased HCO(3)(-) secretion. Interestingly, a small inward current that is sensitive to the anion channel blocker, 5-nitro-2(3-phenylpropyl amino)-benzoate (NPPB), is also activated during cAMP stimulation of the CFTR-null intestine but the identity of the current is yet to be resolved. Studies to identify the proteins involved in non-CFTR mediated HCO(3)(-) secretion are on-going and potentially will provide targets to correct deficient HCO(3)(-) secretion in the CF intestine.
Gériatrie (2022)

Sleeping enough is associated with a reduced risk of mortality and dementia. New evidence support regular physical exercise, including at home, as a corner stone intervention to prevent falls and fractures. In contrast, supplementation with high doses of vitamin D is ineffective and even deleterious in this indication and a routine screening in asymptomatic adults is not recommended. Several studies illustrate our difficulties in prescribing and deprescribing in frail older patients and a study suggests that statins in cardiovascular primary prevention should considered only when a patient's life expectancy exceeds 2.5 years. Finally, several studies have fueled the debate about screening for hearing impairment.
Ethene/alkyne exchange reaction at an intramolecular frustrated Lewis pair (2013)

A vicinal ethylene bridged S/B frustrated Lewis pair (FLP) in situ generated by a hydroboration reaction of phenyl vinyl sulfide, reacts with p-tert-butylphenylacetylene by ethene/alkyne exchange and subsequent 1,2-addition of a second alkyne equivalent to give a zwitterionic sulfonium/borate product.
Abstract A38: Optimization of whole-genome amplification for analysis of single cells using next-generation sequencing (2015)

Abstract The accurate analysis of both genotypic variation in tumors and tumor evolution due to selective pressure is important in determining treatment options in the clinic. Next generation sequencing (NGS) of single cells from solid tumors and circulating tumor cells has the potential to dramatically increase the amount of genotypic detail obtained from these samples. For the analysis of single cells the challenge is to employ whole genome amplification (WGA) to obtain enough DNA for analysis while minimizing amplification bias and maintaining copy accuracy. We are developing tools for single cell sequencing to improve these parameters while also increasing sample throughput. Initially, three commercially available WGA methods were tested on 5-10 genome quantities of HCT-15 genomic DNA. Using the Ion Torrent AmpliSeq Cancer Hotspot Panel, the amplification accuracy, amplicon coverage and DNA yield were determined. When compared to controls significant differences were observed in the three WGA methods ability to accurately amplify DNA. The most accurate kit produced a specificity and sensitivity of 98.5% and 100% respectively. This protocol also produced a substantial DNA yield of 25 µgs and although, the average amplicon coverage indicated some bias, greater than 99% of the amplicons had at least 100-fold coverage. This WGA kit was then tested on single cells from a human breast cancer; an ER/PR/Her2 negative spindle cell metaplastic carcinoma. To obtain single cells the tumor was grown in a PDX mouse model and index sorted using a BD FACSAria II flow cytometer. The WGA produced an average DNA yield of 2.7± 0.8 µg, with 100-fold amplicon coverage of 92±7%. For the variants identified, the amplification bias differed by as much as 3,000 reads/variant. We are now taking steps to improve WGA of single cells and will report on these efforts in detail. To date when monitoring variant allele frequency and coverage depth in the triple negative tumor, KRAS and MET mutations were identified in single cells, as well as in the bulk sample. Interestingly, a TP53 mutation was identified only in single cells. This data supports the utility of WGA and single cell analysis to identify mutations, some having clinically relevant role for targeted therapy. Citation Format: Terry J. Amiss, Frances Tong, Eileen Snowden, Richard Kelly, Rainer Blaesius, Nick Herrmann, Friedrich Hahn, Warren Porter, Mitchell Ferguson, Chen Chang, Daphne Clancy, Stewart Jurgensen. Optimization of whole-genome amplification for analysis of single cells using next-generation sequencing. [abstract]. In: Proceedings of the AACR Precision Medicine Series: Drug Sensitivity and Resistance: Improving Cancer Therapy; Jun 18-21, 2014; Orlando, FL. Philadelphia (PA): AACR; Clin Cancer Res 2015;21(4 Suppl): Abstract nr A38.
Bionic intraocular lens with variable focus and integrated structure (2015)

This paper proposes a bionic accommodating intraocular lens (IOL) for ophthalmic surgery. The designed lens has a solid–liquid mixed integrated structure, which mainly consists of a support ring, elastic membrane, rigid lens, and optical liquid. The lens focus can be adjusted through the deformation of the lens front surface when compressed. The integrated structure of the IOL is presented, as well as a detailed description of the lens materials and fabrication process. Images under different radial pressures are captured, and the lens deformation process, accommodating range, density, and optical property are analyzed. The designed lens achieves a 14.6 D accommodating range under a radial pressure of 51.4 mN and a 0.24 mm alteration of the lens outer radius. The deformation property of the lens matches well with the characteristic of the eye and shows the potential to help patients fully recover their vision accommodation ability after the cataract surgery.
Physicochemical characterization of the gelatin/polycaprolactone nanofibers loaded with diclofenac potassium for topical use aiming potential anti-inflammatory action (2021)

Common adversities as gastrointestinal discomfort are related to conventional administration of diclofenac potassium (DP), and thus the study of a new administration route based on gelatin/polycaprolactone electrospun nanofibers loaded with DP is an innovative way to create biomaterials for topical delivery of drugs aiming the patients’ life quality improvement. SEM-EDS evidenced success in the drug incorporation, while FTIR and DSC indicated possible gelatin and DP interaction. In vitro biodegradation and in vitro release studies showed the gelatin dissolution and dependence of the release profile with the DP wt. % and temperature, respectively. In vitro permeation presented a dermal targeting of DP.
Structure and Bonding of the Multifunctional Amino Acid l-DOPA on Au(110) (2006)

In investigations of the proteins which are responsible for the surface adhesion of the blue mussel Mytilus edulis, an unusually frequent appearance of the otherwise rare amino acid 3-(3,4-dihydroxyphenyl)-L-alanine (L-DOPA) has been observed. This amino acid is thought to play a major role in the mechanism of mussel adhesion. Here we report a detailed structural and spectroscopic investigation of the interface between L-DOPA and a single-crystalline Au(110) model surface, with the aim of understanding fundamentals about the surface bonding of this amino acid and its role in mussel adhesion. Molecular layers are deposited by organic molecular beam deposition (OMBD) in an ultrahigh-vacuum environment. The following experimental techniques have been applied: ex situ Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS), low-energy electron diffraction (LEED), high-resolution electron energy loss spectroscopy (HREELS), and scanning tunneling microscopy (STM). Vibrational spectra of isolated L-DOPA molecules and the zwitterionic bulk have been calculated using density functional theory (DFT). The predicted modes are assigned to observed spectra, allowing conclusions regarding the molecule-substrate and molecule-molecule interactions at the L-DOPA/Au(110) interface. We find that zwitterionic L-DOPA forms a monochiral, one-domain commensurate monolayer on Au(110), with the catechol rings on top of [110] gold rows, oriented parallel to the surface. The (2 x 1)-Au(110) surface reconstruction is not lifted. The carboxylate group is found in a bidentate or bridging configuration, the amino group is tilted out of the surface plane, and the hydroxyl groups do not dehydrogenate on Au(110). Similar to the case for the bulk, molecules form dimers on Au(110). However, the number of hydrogen bridge bonds between L-DOPA molecules is reduced as compared to the bulk. Thicker layers which are deposited onto the commensurate interface do not order in the bulk structure. In conclusion, our study shows that the aromatic ring system of L-DOPA functions as a surface anchor. Since it is also known that the hydroxyl groups support cross-link reactions between L-DOPA residues in the mussel glue protein, we can conclude that the catechol ring supports surface adhesion of mussel proteins via two independent functions.
The combined use of analytical tools for exploring tetanus toxin and tetanus toxoid structures B Analytical technologies in the biomedical and life sciences (2017)

Aldehyde detoxification is a process used to convert toxin into toxoid for vaccine applications. In the case of tetanus toxin (TT), formaldehyde is used to obtain the tetanus toxoid (TTd), which is used either for the tetanus vaccine or as carrier protein in conjugate vaccines. Several studies have already been conducted to better understand the exact mechanism of this detoxification. Those studies led to the identification of a number of formaldehyde-induced modifications on lab scale TTd samples. To obtain greater insights of the changes induced by formaldehyde, we used three industrial TTd batches to identify repeatable modifications in the detoxification process. Our strategy was to combine seven analytical tools to map these changes. Mass spectrometry (MS), colorimetric test and amino acid analysis (AAA) were used to study modifications on amino acids. SDS-PAGE, asymmetric flow field flow fractionation (AF4), fluorescence spectroscopy and circular dichroism (CD) were used to study formaldehyde modifications on the whole protein structure. We identified 41 formaldehyde-induced modifications across the 1315 amino acid primary sequence of TT. Of these, five modifications on lysine residues were repeatable across TTd batches. Changes in protein conformation were also observed using SDS-PAGE, AF4 and CD techniques. Each analytical tool brought a piece of information regarding formaldehyde induced-modifications, and all together, these methods provided a comprehensive overview of the structural changes that occurred with detoxification. These results could be the first step leading to site-directed TT mutagenesis studies that may enable the production of a non-toxic equivalent protein without using formaldehyde.
Wolbachia w Stri Blocks Zika Virus Growth at Two Independent Stages of Viral Replication (2018)

Mosquito-transmitted viruses are spread globally and present a great risk to human health. Among the many approaches investigated to limit the diseases caused by these viruses are attempts to make mosquitos resistant to virus infection. Coinfection of mosquitos with the bacterium <i>Wolbachia pipientis</i> from supergroup A is a recent strategy employed to reduce the capacity for major vectors in the <i>Aedes</i> mosquito genus to transmit viruses, including dengue virus (DENV), Chikungunya virus (CHIKV), and Zika virus (ZIKV). Recently, a supergroup B <i>Wolbachia w</i>Stri, isolated from <i>Laodelphax striatellus</i>, was shown to inhibit multiple lineages of ZIKV in <i>Aedes albopictus</i> cells. Here, we show that <i>w</i>Stri blocks the growth of positive-sense RNA viruses DENV, CHIKV, ZIKV, and yellow fever virus by greater than 99.9%. <i>w</i>Stri presence did not affect the growth of the negative-sense RNA viruses LaCrosse virus or vesicular stomatitis virus. Investigation of the stages of the ZIKV life cycle inhibited by <i>w</i>Stri identified two distinct blocks in viral replication. We found a reduction of ZIKV entry into <i>w</i>Stri-infected cells. This was partially rescued by the addition of a cholesterol-lipid supplement. Independent of entry, transfected viral genome was unable to replicate in <i>Wolbachia</i>-infected cells. RNA transfection and metabolic labeling studies suggested that this replication defect is at the level of RNA translation, where we saw a 66% reduction in mosquito protein synthesis in <i>w</i>Stri-infected cells. This study's findings increase the potential for application of <i>w</i>Stri to block additional arboviruses and also identify specific blocks in viral infection caused by <i>Wolbachia</i> coinfection.<b>IMPORTANCE</b> Dengue, Zika, and yellow fever viruses are mosquito-transmitted diseases that have spread throughout the world, causing millions of infections and thousands of deaths each year. Existing programs that seek to contain these diseases through elimination of the mosquito population have so far failed, making it crucial to explore new ways of limiting the spread of these viruses. Here, we show that introduction of an insect symbiont, <i>Wolbachia w</i>Stri, into mosquito cells is highly effective at reducing yellow fever virus, dengue virus, Zika virus, and Chikungunya virus production. Reduction of virus replication was attributable to decreases in entry and a strong block of virus gene expression at the translational level. These findings expand the potential use of <i>Wolbachia w</i>Stri to block viruses and identify two separate steps for limiting virus replication in mosquitos that could be targeted via microbes or other means as an antiviral strategy.
Programmable Electrowetting Channels (2010)

A new mechanism for electrical creation of liquid channels is presented. These channels have the advantages of programmability and continuous channel functionality.
Malate dehydrogenase from the thermophilic green bacterium Chloroflexus aurantiacus: purification, molecular weight, amino acid composition, and partial amino acid sequence (1988)

Malate dehydrogenase (MDH; EC 1.1.1.37) from the thermophilic green nonsulfur bacterium Chloroflexus aurantiacus was purified by a two-step procedure involving affinity chromatography and gel filtration. The enzyme consists of identical subunits which had molecular weights of approximately 35,000. In its active form at 55 degrees C, it formed tetramers. At lower temperatures, inactive dimers and trimers existed. Antibodies against the purified enzyme were produced, and immunotitration and enzyme-linked immunosorbent assays showed that there was an immunochemical homology between the MDH from C. aurantiacus and MDHs from several other bacteria. The amino acid composition of C. aurantiacus MDH was similar to those of other MDHs. The N-terminal amino acid sequence was enriched with hydrophobic amino acids, which showed a high degree of functional similarity to amino acids at the N-terminal ends of both Escherichia coli and Thermus flavus MDHs. The activity of the native enzyme was inhibited by high concentrations of substrate and had temperature and pH optima consistent with the optimal growth conditions for the organism.
Treatment of experimental autoimmune encephalomyelitis with antisense oligonucleotides against the low affinity neurotrophin receptor (2000)

Upregulated expression of the low-affinity neurotrophin receptor (p75) in the central nervous system (CNS) during experimental autoimmune encephalomyelitis (EAE) has recently been demonstrated. To investigate whether p75 plays a role in disease pathogenesis, we adopted a gene therapy approach, utilizing antisense oligonucleotides to downregulate p75 expression during EAE. Phosphorothioate antisense oligonucleotides (AS), nonsense oligonucleotides (NS) or phosphate buffered saline (PBS) were injected daily for 18 days after immunization of SJL/J (H-2s)-mice with myelin proteolipid protein (PLP) peptide 139-151. In the AS group, there was a statistically significant reduction in both the mean maximal disease score (1.85 in the AS, 2.94 in the NS and 2.75 in the PBS-groups, respectively, P < 0.025) and in the cumulative disease incidence ( approximately 60% in the AS group and approximately 90% in the control groups). Histological and immunohistochemical analysis showed reduced inflammation and demyelination, as well as reduced p75 expression at the blood-brain barrier (BBB) in the AS-treated mice in comparison with both control groups. There was no difference, however, in p75 expression on neural cells within the CNS between the three groups of mice. We conclude that p75 could play a proactive role in the pathogenesis of EAE and may exert its effect at the level of the BBB.
Directionality and Integration of Nanoscale Plasmon Lasers (2012)

We demonstrated the first directionally emitting deep sub-wavelength plasmon laser and circuit. The plasmon laser circuit naturally integrates photonic and electronic functionality allowing both efficient electrical modulation and wavelength multiplexing.
Performance Evaluation of a Portable Restraint for a Motor Coach Occupant in a Rollover Accident (2009)

A quarter roll of a motor coach could result in fatal injuries to its occupants due to ejection and occupants striking each other and striking the bus interior. The best rational solution to prevent ejection and serious head injury is to restrain the occupants to their seats. This study addresses the dynamic performance of the portable restraint in a rollover accident and compares it to the conventional restraint. The biodynamic code MADYMO is used to analyze and compare the occupant kinematic with the portable restraint and the conventional restraint. The full scale bus rollover motion data with different ATD’s (Anthropomorphic test devices) placed at different locations on the bus shall be used to prescribe motion to this MADYMO model. This study demonstrates the success of the portable restraint in preventing ejections if the lateral belt used for securing the system to the seat does not slip. The study further demonstrates the possibility of improving the portable restraint performance using computational model.
On the topologies formed by selfish peers (2006)

Current peer-to-peer (P2P) systems often suffer from a large fraction of freeriders not contributing any resources to the network. Various mechanisms have been designed to overcome this problem. However, the selfish behavior of peers has aspects which go beyond resource sharing. This paper studies the effects on the topology of a P2P network if peers selfishly select the peers to connect to. In our model, a peer exploits locality properties in order to minimize the latency (or response times) of its lookup operations. At the same time, the peer aims at not having to maintain links to too many other peers in the system. By giving tight bounds on the price of anarchy, we show that the resulting topologies can be much worse than if peers collaborated. Moreover, the network may never stabilize, even in the absence of churn. Finally, we establish the complexity of Nash equilibria in our game theoretic model of P2P networks. Specifically, we prove that it is NP-hard to decide whether our game has a Nash equilibrium and can stabilize.
Binary gratings with increased efficiency (1992)

Coupled-wave analysis is used to design binary gratings with high efficiencies (70-80%). The binary designs have grating periods greater than one wavelength but use subwavelength structures within each period in order to achieve high efficiency.
Nanomaterials for Energy Applications (2017)

A wide variety of nanomaterials have been applied to energy related applications, including nanofibers, nanocrystalline materials, nanoparticles, and thin film nanocoatings. Solid-state lighting offers significant advantages in energy efficiency compared to traditional lighting technologies. The potential for nanostructured solid-state lighting devices is excellent as it enjoys significant economic drivers in energy efficiency. Fuel cells convert chemical energy to electrical energy through electrochemical reactions at an anode and cathode. The conversion of biomass to fuels and chemicals offers great potential to reduce energy dependence on petroleum and reduce green house gas emissions. Batteries involve the production and storage of electrical charge, the transfer of cations and electrical current, each based on electrochemical reactions and chemical reactants. Battery performance relies on the complex processes and factors that affect the transport of charge in the reactants, and across the interface between the chemical phases.
Uncertainty Assessment on Well-Performance Prediction for an Oil Producer Equipped With Selected Completions (2007)

Abstract In order to make an appropriate business decision on well completion, the impacts of uncertainty of key completion parameters on well performance must be carefully evaluated to reasonably estimate the well performance. A procedure has been proposed for the evaluation purpose. The procedure will be applied to five common types of well completions to illustrate the importance of the proposed uncertainty analysis. A field case study will be discussed in detail in the paper to demonstrate the uncertainty assessment process for efficient completion designs. The case study will be focused on a horizontal oil producer where different completion options have been proposed. The relative impacts of different parameters on the well production will be investigated to identify the major parameters that could affect the well production the most. The field case study will help us to understand the importance of the uncertainty analysis and its potential impacts on the final completion selection.