gebhart/patrepeval huggingface dataset:
Dystrophin is transcribed in brain from a distant upstream promoter. (1991)

Dystrophin, the protein product of the Duchenne muscular dystrophy gene, is expressed in brain as well as muscle. The role of dystrophin in the brain is not clear, though one-third of Duchenne muscular dystrophy patients exhibit some degree of mental retardation. We have isolated the genomic region encoding the alternative 5' terminus of dystrophin used in the brain. Primer extension and polymerase chain reaction assays on RNA demonstrate that this region contains an alternative promoter for dystrophin used in the brain. Physical mapping of this region indicates that this brain promoter is located greater than 90 kilobases 5' to the promoter used in muscle and 400 kilobases from exon 2 to which it is spliced. The large physical distance between the promoters, taken together with their known tissue selectivities, suggests that in certain patients a deletion of either dystrophin promoter might give rise to reduced dystrophin expression selective to brain or muscle. We have identified one such individual with specific deletion of the dystrophin muscle promoter, giving rise to Becker muscular dystrophy, and we predict that specific loss of the brain promoter may be one cause of X chromosome-linked mental retardation.
Emigration of monocyte-derived cells from atherosclerotic lesions characterizes regressive, but not progressive, plaques (2004)

Some monocytes normally take up residence in tissues as sessile macrophages, but others differentiate into migratory cells resembling dendritic cells that emigrate to lymph nodes. In an in vitro model of a vessel wall, lipid mediators lysophosphatidic acid and platelet-activating factor, whose signals are implicated in promoting atherosclerosis, blocked conversion of monocytes into migratory cells and favored their retention in the subendothelium. In vivo studies revealed trafficking of monocyte-derived cells from atherosclerotic plaques during lesion regression, but little emigration was detected from progressive plaques. Thus, progression of atherosclerotic plaques may result not only from robust monocyte recruitment into arterial walls but also from reduced emigration of these cells from lesions.
Zinc-finger nuclease-driven targeted integration into mammalian genomes using donors with limited chromosomal homology (2010)

We previously demonstrated high-frequency, targeted DNA addition mediated by the homology-directed DNA repair pathway. This method uses a zinc-finger nuclease (ZFN) to create a site-specific double-strand break (DSB) that facilitates copying of genetic information into the chromosome from an exogenous donor molecule. Such donors typically contain two approximately 750 bp regions of chromosomal sequence required for homology-directed DNA repair. Here, we demonstrate that easily-generated linear donors with extremely short (50 bp) homology regions drive transgene integration into 5-10% of chromosomes. Moreover, we measure the overhangs produced by ZFN cleavage and find that oligonucleotide donors with single-stranded 5' overhangs complementary to those made by ZFNs are efficiently ligated in vivo to the DSB. Greater than 10% of all chromosomes directly incorporate this exogenous DNA via a process that is dependent upon and guided by complementary 5' overhangs on the donor DNA. Finally, we extend this non-homologous end-joining (NHEJ)-based technique by directly inserting donor DNA comprising recombinase sites into large deletions created by the simultaneous action of two separate ZFN pairs. Up to 50% of deletions contained a donor insertion. Targeted DNA addition via NHEJ complements our homology-directed targeted integration approaches, adding versatility to the manipulation of mammalian genomes.
Ellipsometric Approach for the Real-Time Detection of Label-Free Protein Adsorption by Second Harmonic Generation (2004)

Second harmonic generation (SHG) was performed using a novel ellipsometric detection approach to selectively probe the real-time surface binding kinetics of an unlabeled protein. The coherence of nonlinear optical processes introduces new possibilities for exploiting polarization that are unavailable with incoherent methods, such as absorbance and fluorescence. Adsorption of bovine serum albumin (BSA) at silica/aqueous solution interfaces resulted in changes in the polarization state of the frequency-doubled light through weak, dynamic interactions with a coadsorbed nonlinear optical probe molecule (rhodamine 6G). Using a remarkably simple instrumental approach, signals arising exclusively from surface interactions with BSA were spatially isolated and selectively detected with high signal-to-noise. The relative intensities acquired during the kinetics experiments using both circularly and linearly polarized incident beams were in excellent agreement with the responses predicted from SHG ellipsometry polarization measurements. Analysis of the polarization-dependent SHG generated during BSA adsorption at glass/aqueous solution interfaces provided direct evidence for slow conformational changes within the protein layer after adsorption, consistent with protein denaturation. This polarization selection approach is sufficiently general to be easily extended to virtually all coherent nonlinear optical processes and a variety of different surface interactions and architectures.
Antiperspirants and the hyperhidrosis patient (2001)

Hyperhidrosis is the production of excess sweat of the armpits, hands, feet, or face. The sweating can be simply unsightly or a true impairment to the optimal functioning of children and adults. This dermatologic problem can be treated with topical antiperspirants, oral medications, or by injections of botulinum toxin. This article examines the physiology of sweat reduction and the efficacy of various therapies, and presents a practical approach for the treatment of this condition.
Interaction of bilirubin and biliverdin with reactive nitrogen species (2003)

Bilirubin (BR) and biliverdin (BV), two metabolites produced during haem degradation by haem oxygenase, possess strong antioxidant activities toward peroxyl radical, hydroxyl radical and hydrogen peroxide. Considering the importance attributed to nitric oxide (NO) and its congeners in the control of physiological and pathophysiological processes, we examined the interaction of BR and BV with NO and NO-related species in vitro. Exposure of BR and BV to agents that release NO or nitroxyl resulted in a concentration- and time-dependent loss of BR and BV, as assessed by high performance liquid chromatography. Peroxynitrite, a strong oxidant derived from the reaction of NO with superoxide anion, also showed high reactivity toward BR and BV. The extent of BR and BV consumption largely depended on the NO species being analysed and on the half-lives of the pharmacological compounds considered. Of major importance, BR and BV decomposition occurred also in the presence of pure NO under anaerobic conditions, confirming the ability of bile pigments to scavenge the gaseous free radical. Increasing concentrations of thiols prevented BR consumption by nitroxyl, indicating that bile pigments and thiol groups can compete and/or synergise the cellular defence against NO-related species. In view of the high inducibility of haem oxygenase-1 by NO-releasing agents in different cell types, the present findings highlight novel anti-nitrosative characteristics of BR and BV suggesting a potential function for bile pigments against the damaging effects of uncontrolled NO production.
Molecular analysis of the emergence of pandemic Vibrio parahaemolyticus (2008)

Our data show that there is considerable genomic flux in this species and that the new highly virulent clone arose from an O3:K6 isolate that acquired at least seven novel regions, which included both a T3SS and a T6SS.
Defective regulation of energy metabolism in mdx-mouse skeletal muscles (1994)

Our previous finding of a reduced energy metabolism in slow- and fast-twitch skeletal muscle fibres from the murine model of Duchenne muscular dystrophy (the mdx mouse) led us to examine the importance of intracellular glucose availability for a normal energy turnover. To this end, basal and KCl-stimulated (20.9 mM total extracellular K+) rates of glucose uptake (GUP) and heat production were measured in isolated, glucose-incubated (5 mM) soleus and extensor digitorum longus muscles from mdx and control C57B1/10 mice, in the presence and in the absence of insulin (1.7 nM). Under all conditions and for both muscle types, glucose uptake values for mdx and control muscles were similar although heat production was lower in mdx muscles. The marked stimulation of GUP by insulin in both mdx and control muscles had only minor effects on heat production. In contrast, glucose deprivation or inhibition of glycolysis with 2-deoxy-D-glucose (5 mM) significantly decreased heat production in control muscles only, which attenuated, although did not suppress, the difference in basal heat production between mdx and control muscles. Stimulation of heat production by a short-chain fatty acid salt (octanoate, 2 mM) was significantly less marked in mdx than in control muscles. Increased cytoplasmic synthesis of CoA by addition of 5 mM pantothenate (vitamin B5) increased the thermogenic response to glucose more in mdx than in control muscles. We conclude that the low energy turnover in mdx-mouse muscle fibres is not due to a decrease of intracellular glucose availability, but rather to a decreased oxidative utilization of glucose and free fatty acids. We suggest that some enzyme complex of the tricarboxylic acid cycle or inefficiency of CoA transport in the mitochondria could be involved.
4-Methoxybenzyloxymethyl Group, a Racemization-Resistant Protecting Group for Cysteine in Fmoc Solid Phase Peptide Synthesis (2012)

The 4-methoxybenzyloxymethyl (MBom) group was introduced for sulfhydryl protection of Cys in combination with Fmoc chemistry. The MBom group proved to substantially suppress racemization of Cys during its incorporation mediated by phosphonium or uronium reagents. Furthermore, this group was found to significantly reduce racemization of the C-terminal Cys linked to a hydroxyl resin during repetitive base treatment, in comparison with the usually used trityl (Trt) and acetamidomethyl (Acm) groups.
Bright, Crack-Free InGaN/GaN Light Emitters on Si(111) (2002)

Crack-free, up to 2.8 μm thick GaN-based light emitting diodes were grown by metalorganic chemical vapor deposition on 2-inch Si(111) substrates. Elimination of cracks was achieved by using two ∼12 nm thick low-temperature AlN : Si interlayers for stress reduction. A significant enhancement in optical output power was obtained by an in situ insertion of a SixNy mask. Transmission electron microscopy measurements showed a tenfold reduction in dislocation density to ∼109 cm—2 by the low-temperature AlN and SixNy interlayers, resulting in a significant increase in luminescence intensity. Vertically contacted diodes showed a light output power of 152 <$>\mmu<$>W at a current of 20 mA and a wavelength of 455 nm. Turn-on voltages around 2.8 V and series resistances of 55 Ω were obtained.
Isolation of Arabidopsis Mutants With Enhanced Disease Susceptibility by Direct Screening (1996)

To discover which components of plant defense responses make significant contributions to limiting pathogen attack, we screened a mutagenized population of Arabidopsis thaliana for individuals that exhibit increased susceptibility to the moderately virulent bacterial pathogen Pseudomonas syringae pv. maculicola ES4326 (Psm ES4326). The 12 enhanced disease susceptibility (eds) mutants isolated included alleles of two genes involved in phytoalexin biosynthesis (pad2, which had been identified previously, and pad4, which had not been identified previously), two alleles of the previously identified npr1 gene, which affects expression of other defense genes, and alleles of seven previously unidentified genes of unknown function. The npr1 mutations caused greatly reduced expression of the PR1 gene in response to PsmES4326 infection, but had little effect on expression of two other defense genes, BGL2 and PR5, suggesting that PR1 expression may be important for limiting growth of PsmES4326. While direct screens for mutants with quantitative pathogen-susceptibility phenotypes have not been reported previously, our finding that mutants isolated in this way include those affected in known defense responses supports the notion that this type of screening strategy allows genetic dissection of the roles of various plant defense responses in disease resistance.
Non-Invasive Prenatal Testing of Trisomy 18 by an Epigenetic Marker in First Trimester Maternal Plasma (2013)

Our results suggest that U-maspin and M-maspin concentrations may be useful as potential biomarkers for non-invasive detection of fetal trisomy 18 in the first trimester of pregnancy, irrespective of the sex and genetic variations of the fetus.
Cas5d processes pre-crRNA and is a member of a larger family of CRISPR RNA endonucleases (2012)

Small RNAs derived from clustered, regularly interspaced, short palindromic repeat (CRISPR) loci in bacteria and archaea are involved in an adaptable and heritable gene-silencing pathway. Resistance to invasive genetic material is conferred by the incorporation of short DNA sequences derived from this material into the genome as CRISPR spacer elements separated by short repeat sequences. Processing of long primary transcripts (pre-crRNAs) containing these repeats by a CRISPR-associated (Cas) RNA endonuclease generates the mature effector RNAs that target foreign nucleic acid for degradation. Here we describe functional studies of a Cas5d ortholog, and high-resolution structural studies of a second Cas5d family member, demonstrating that Cas5d is a sequence-specific RNA endonuclease that cleaves CRISPR repeats and is thus responsible for processing of pre-crRNA. Analysis of the structural homology of Cas5d with the previously characterized Cse3 protein allows us to model the interaction of Cas5d with its RNA substrate and conclude that it is a member of a larger family of CRISPR RNA endonucleases.
Comparative study on artificial neural network with multiple regressions for continuous estimation of blood pressure (2005)

There are many studies about cuffless and continuous blood pressure estimation using pulse transit time (PTT). In this study, we proposed the modeling method which could estimate systolic BP (SBP) conveniently and indirectly using PTT and some biometric parameters. 45 people participated in this study and we measured PTT using photoplethysmography (PPG) and electrocardiogram (ECG) signals and biometric parameters such as weight, height, body mass index (BMI), length of arm and circumference of arm. Before modeling, we selected variables as predictors using statistical analysis. With these parameters, we compared artificial neural network (ANN) with multiple regressions as an estimating method of BP. We evaluated the mean differences and standard deviations between estimated value and reference value, acquired from a KEDA-approved device. The results showed that the ANN had better accuracy than the multiple regression. ANN's estimation satisfied AAMI standard as a BP device.
Rotating frame zeugmatography (1980)

The proton sensitivity obtainable at 5 MHz from a baby is sufficiently large to suggest the possibility of obtaining images with millimetre solution in seconds. Such goals present difficulties; for example, the high quality factor of the receiving coil necessary for good sensitivity limits the receiver bandwidth and leads to long pulse recovery times, and large, rapidly switched field gradients require power engineering. Solutions to these problems are being pursued at the National Institutes of Health (N.I.H.), where a high speed imaging system is under construction. For example, bandwidth and recovery time problems may be resolved with the aid of a low noise preamplifier with imaginary gain and Miller feedback, large gradients may be generated with a magnet comprising two rotatable hemispherical windings and switching of gradients may be eliminated by performing zeugmatography in the rotating frame. It is upon this latter aspect of the design that the present article concentrates.
Donor Diffusion Dynamics in Silicon (1971)

Arsenic, antimony, and bismuth have been diffused into (111) silicon from doped expitaxially deposited source layers in a flowing hydrogen atmosphere. Under intrinsic conditions, the dopant profiles show excellent Fickian behavior. The diffusion coefficients, obtained as a function of temperature, can be described by the following equations: ${D}_{\mathrm{As}}=6.55\ifmmode\times\else\texttimes\fi{}{10}^{\ensuremath{-}2}\ifmmode\times\else\texttimes\fi{}\frac{\mathrm{exp}(\ensuremath{-}3.44\ifmmode\pm\else\textpm\fi{}0.04 \mathrm{eV})}{\mathrm{kT}}$ ${\mathrm{cm}}^{2}$/sec; ${D}_{\mathrm{Sb}}=2.14\ifmmode\times\else\texttimes\fi{}{10}^{\ensuremath{-}1}\frac{\mathrm{exp}(\ensuremath{-}3.65\ifmmode\pm\else\textpm\fi{}0.05 \mathrm{eV})}{\mathrm{kT}}$ ${\mathrm{cm}}^{2}$/sec; and ${D}_{\mathrm{Bi}}=1.08\frac{\mathrm{exp}(\ensuremath{-}3.85\ifmmode\pm\else\textpm\fi{}0.06 \mathrm{eV})}{\mathrm{kT}}$ ${\mathrm{cm}}^{2}$/sec. These data, together with those of phosphorus reported earlier, are shown to be consistent with a point-defect mechanism that involves a closely coupled vacancy-impurity ensemble.
Interaction of cyanine dyes with nucleic acids. XXI. Arguments for half‐intercalation model of interaction (2001)

The spectral luminescent properties of two groups of monomethine cyanine dyes were studied in the presence of DNA. The first group included five dyes with 5,6-methylenedioxy-[d]-benzo-1,3-thiazole heterocycle and their unsubstituted analogs. Five monomethine pyrylium cyanines and their N-methyl-pyridine analogs were included in the second group. In each pair the pyrylium and pyridine dyes had similar geometry but differed in charge density distribution. The results presented some evidence in favor of the half-intercalation interaction mode between the studied dyes and DNA. When the benzothiazole residue had the lowest electron donor ability between the two heterocycles in the dye molecule, its substitution with the bulky methylenedioxy group led to a significant decrease in fluorescence enhancement of the dye-DNA complex. On the contrary, when the substituents that create steric hindrance (e.g., methylenedioxy and methyl groups) were introduced into the heterocycle with the higher electron donor ability, the fluorescence enhancement value of the dye-DNA complex was virtually unchanged. The changes in the Stock's shift values upon the formation of the dye-DNA complexes were in agreement with the proposed half-intercalation model. Interestingly, in the dye-DNA complexes the pyrylium dyes probably resided in a place similar to the pyridine ones. It is possible that the benzothiazole (or benzooxazole) ring intercalated between the DNA bases and the pyrylium (or pyridine) residue was located in the DNA groove closer to the phosphate backbone.
Treatment of Stargardt disease with dobesilate (2012)

Stargardt disease is a common inherited macular degeneration characterised by a significant loss in the central vision during the first or second decade of the life. Bilateral atrophic changes in the central retina are associated with degeneration of photoreceptors and underlying retinal pigment epithelium, and yellow flecks are extending from the macula. We present a patient with Stargardt disease treated with an intravitreal injection of dobesilate, showing an improvement of visual acuity 4 weeks after treatment.
Design aspects of superconducting-phase quantum bits (2001)

A superconducting-phase quantum bit (qubit) involves three or more Josephson junctions combined into a superconducting loop and defines one of the promising solid-state device implementations for quantum computing. Recently, so called $\ensuremath{\pi}$ junctions, Josephson junctions with a ground state characterized by a \ensuremath{\pi}-phase shift across, have attracted much attention. We show how to make use of such $\ensuremath{\pi}$ junctions in the construction of superconducting phase qubits and discuss the advantage over conventional designs based on magnetically frustrated loops. Starting from a basic five-junction loop with one $\ensuremath{\pi}$ junction, we show how to construct effective junctions with degenerate minima characterized by phase shifts 0 and $\ensuremath{\pi}$ and superconducting-phase switches. These elements are then combined into a superconducting-phase qubit which operates exclusively with switches, thus avoiding permanent contact with the environment through external biasing. The resulting superconducting-phase qubits can be understood as the macroscopic analog of the ``quiet'' s-wave--d-wave--s-wave Josephson-junction qubits introduced by Ioffe et al. [Nature (London) 398, 679 (1999)].
Myelin autoreactivity in multiple sclerosis: recognition of myelin basic protein in the context of HLA-DR2 products by T lymphocytes of multiple-sclerosis patients and healthy donors. (1990)

A panel of 20 human myelin basic protein (hMBP)-specific T-lymphocyte lines was generated from the peripheral blood of eight multiple sclerosis (MS) patients and two healthy donors, most of them expressing the HLA-DR2 haplotype, which is associated with an increased susceptibility to MS. Using HLA-DR gene-transfected mouse L-cell lines as antigen-presenting cells, we established that of the 20 hMBP-specific T-lymphocyte lines, 7 were restricted by the DR2a gene products of the DR2Dw2 haplotype. Four T-cell lines recognized hMBP in the context of the DR2b products of the DR2Dw2 haplotype. DR2b-restricted T-cell responses were demonstrable only in T-cell lines derived from MS patients. The hMBP epitopes presented by the DR2a heterodimer were mapped to peptides covering amino acid residues 1-44, 76-91, 131-145, or 139-153 and to a region spanning the thrombin-cleaved bond at Arg130-Ala131. DR2b-restricted T-cell lines recognized epitopes within amino acids 80-99 and 148-162. Peptide 139-153 was also presented in the context of HLA-DR1 molecules. Our data show that (i) in MS patients both the DR2a and DR2b products of the DR2Dw2 haplotype function as restriction elements for the myelin autoantigen hMBP, (ii) the DR2a molecule presents at least five different epitopes to hMBP-specific T lymphocytes, and (iii) anti-hMBP T-cell lines derived from individual donors can differ in their antigen fine specificity as well as in their HLA restriction.
Strategies to induce broadly protective antibody responses to viral glycoproteins (2017)

Currently, several universal/broadly protective influenza virus vaccine candidates are under development. Many of these vaccines are based on strategies to induce protective antibody responses against the surface glycoproteins of antigenically and genetically diverse influenza viruses. These strategies might also be applicable to surface glycoproteins of a broad range of other important viral pathogens. Areas covered: Common strategies include sequential vaccination with divergent antigens, multivalent approaches, vaccination with glycan-modified antigens, vaccination with minimal antigens and vaccination with antigens that have centralized/optimized sequences. Here we review these strategies and the underlying concepts. Furthermore, challenges, feasibility and applicability to other viral pathogens are discussed. Expert commentary: Several broadly protective/universal influenza virus vaccine strategies will be tested in humans in the coming years. If successful in terms of safety and immunological readouts, they will move forward into efficacy trials. In the meantime, successful vaccine strategies might also be applied to other antigenically diverse viruses of concern.