gebhart/patrepeval huggingface dataset:
Targets of somatic hypermutation within immunoglobulin light chain genes in zebrafish (2010)

In mammals, somatic hypermutation (SHM) of immunoglobulin (Ig) genes is critical for the generation of high-affinity antibodies and effective immune responses. Knowledge of sequence-specific biases in the targeting of somatic mutations can be useful for studies aimed at understanding antibody repertoires produced in response to infections, B-cell neoplasms, or autoimmune disease. To evaluate potential nucleotide targets of somatic mutation in zebrafish (Danio rerio), an enriched IgL cDNA library was constructed and > 250 randomly selected clones were sequenced and analysed. In total, 55 unique VJ-C sequences were identified encoding a total of 125 mutations. Mutations were most prevalent in V(L) with a bias towards single base transitions and increased mutation in the complementarity-determining regions (CDRs). Overall, mutations were overrepresented at WRCH/DGYW motifs suggestive of activation-induced cytidine deaminase (AID) targeting which is common in mice and humans. In contrast to mammalian models, N and P addition was not observed and mutations at AID hotspots were largely restricted to palindromic WRCH/DGYW motifs. Mutability indexes for di- and trinucleotide combinations confirmed C/G targets within WRCH/DGYW motifs to be statistically significant mutational hotspots and showed trinucleotides ATC and ATG to be mutation coldspots. Additive mutations in VJ-C sequences revealed patterns of clonal expansion consistent with affinity maturation responses seen in higher vertebrates. Taken together, the data reveal specific nucleotide targets of SHM in zebrafish and suggest that AID and affinity maturation contribute to antibody diversification in this emerging immunological model.
Fast approximate energy minimization via graph cuts (2001)

Many tasks in computer vision involve assigning a label (such as disparity) to every pixel. A common constraint is that the labels should vary smoothly almost everywhere while preserving sharp discontinuities that may exist, e.g., at object boundaries. These tasks are naturally stated in terms of energy minimization. The authors consider a wide class of energies with various smoothness constraints. Global minimization of these energy functions is NP-hard even in the simplest discontinuity-preserving case. Therefore, our focus is on efficient approximation algorithms. We present two algorithms based on graph cuts that efficiently find a local minimum with respect to two types of large moves, namely expansion moves and swap moves. These moves can simultaneously change the labels of arbitrarily large sets of pixels. In contrast, many standard algorithms (including simulated annealing) use small moves where only one pixel changes its label at a time. Our expansion algorithm finds a labeling within a known factor of the global minimum, while our swap algorithm handles more general energy functions. Both of these algorithms allow important cases of discontinuity preserving energies. We experimentally demonstrate the effectiveness of our approach for image restoration, stereo and motion. On real data with ground truth, we achieve 98 percent accuracy.
The Modified Kaluza Synthesis. III. The Synthesis of Some Aromatic Isothiocyanates (1964)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTThe Modified Kaluza Synthesis. III. The Synthesis of Some Aromatic IsothiocyanatesJoe E. Hodgkins and W. Preston ReevesCite this: J. Org. Chem. 1964, 29, 10, 3098–3099Publication Date (Print):October 1, 1964Publication History Published online1 May 2002Published inissue 1 October 1964https://doi.org/10.1021/jo01033a524RIGHTS & PERMISSIONSArticle Views1081Altmetric-Citations111LEARN 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 (258 KB) Get e-Alerts Get e-Alerts
CYP707A1 and CYP707A2, Which Encode Abscisic Acid 8′-Hydroxylases, Are Indispensable for Proper Control of Seed Dormancy and Germination in Arabidopsis (2006)

Endogenous abscisic acid (ABA) levels are regulated by both biosynthesis and catabolism of the hormone. ABA 8'-hydroxylase is considered to be the key catabolic enzyme in many physiological processes. We have previously identified that four members of the Arabidopsis (Arabidopsis thaliana) CYP707A gene family (CYP707A1 to CYP707A4) encode ABA 8'-hydroxylases, and that the cyp707a2 mutants showed an increase in ABA levels in dry and imbibed seeds. In this study, we showed that the cyp707a1 mutant accumulated ABA to higher levels in dry seeds than the cyp707a2 mutant. Expression analysis showed that the CYP707A1 was expressed predominantly during mid-maturation and was down-regulated during late-maturation. Concomitantly, the CYP707A2 transcript levels increased from late-maturation to mature dry seed. Phenotypic analysis of single and double cyp707a mutants indicates that the CYP707A1 is important for reducing ABA levels during mid-maturation. On the other hand, CYP707A2 is responsible for the regulation of ABA levels from late-maturation to germination. Moreover, CYP707A1 and CYP707A3 were also shown to be involved in postgermination growth. Spatial expression analysis suggests that CYP707A1 was expressed predominantly in embryo during mid-maturation, whereas CYP707A2 expression was detected in both embryo and endosperm from late-maturation to germination. Our results demonstrate that each CYP707A gene plays a distinct role during seed development and postgermination growth.
Quantifying the interaction of an ocean bottom seismometer with the seabed (1998)

A theory is presented for the coupling between an ocean bottom seismometer (OBS), the sediments upon which it rests, and the surrounding water. Assuming that rotational and tilt effects are negligible (or have been made negligible through instrument design), the response of the OBS to forced harmonic motion is considered in both horizontal and vertical directions. Under these conditions it is concluded that the measured ratio of velocities when the OBS is on the seabed and when it is freely suspended in water (for an identical force) completely characterizes the OBS/seabed interaction. This enables the velocity transfer functions to be directly calculated without recourse to a detailed model of sediment/structure interaction. An OBS was designed and constructed with good coupling to seabed motion and reduction of rocking effects as principal design criteria, including an onboard shaker to conduct in situ coupling experiments. The amplitude and phase of coupling data collected on a clay seabed provide transfer functions due to horizontal and vertical seabed motion and horizontal water motion. In addition, a simple mass‐spring‐dashpot model of OBS/seabed interaction permits the analysis of amplitude‐only coupling data. Good vertical coupling can be achieved over a wide bandwidth by designing the sensor package to have a large hydrodynamic added mass in the vertical. Good coupling to horizontal seabed motion is more difficult to achieve but is possible within a limited bandwidth, even on very soft seabeds. Finally, an example of seismoacoustic noise is presented. Hydrophone signals are compared with horizontal geophone signals received from sources within the ocean and within the seabed, and the differences are explained in terms of the coupling transfer functions.
The Horizon of a Therapy for Rare Genetic Diseases: A “Druggable” Future for Fibrodysplasia Ossificans Progressiva (2018)

Fibrodysplasia ossificans progressiva (FOP) is a rare genetic condition characterized by progressive extra-skeletal ossification leading to cumulative and severe disability. FOP has an extremely variable and episodic course and can be induced by trauma, infections, iatrogenic harms, immunization or can occur in an unpredictable way, without any recognizable trigger. The causative gene is <i>ACVR1</i>, encoding the Alk-2 type I receptor for bone morphogenetic proteins (BMPs). The signaling is initiated by BMP binding to a receptor complex consisting of type I and II molecules and can proceed into the cell through two main pathways, a canonical, SMAD-dependent signaling and a p38-mediated cascade. Most FOP patients carry the recurrent R206H substitution in the receptor Glycine-Serine rich (GS) domain, whereas a few other mutations are responsible for a limited number of cases. Mutations cause a dysregulation of the downstream BMP-dependent pathway and make mutated ACVR1 responsive to a non-canonical ligand, Activin A. There is no etiologic treatment for FOP. However, many efforts are currently ongoing to find specific therapies targeting the receptor activity and the downstream aberrant pathway at different levels or targeting cellular components and/or processes that are important in modifying the local environment leading to bone neo-formation.
<title>Frozen-solution MALDI mass spectrometry studies of DNA</title> (1996)

Matrix-assisted laser desorption/ionization (MALDI) in conjunction with time-of-flight mass spectrometry is an effective technique for analysis of DNA oligomers. However, with increasing oligomer length, mass resolution and sensitivity degrade as the effects of prompt and metastable decay, adduct formation, and ion kinetic energy spreads become increasingly dominant. Attempts to reduce these factors have focused on the use of volatile liquids as matrices because these molecules have lower binding energies both to themselves and to the DNA and theoretically require less energy for desorption. We have investigated thin films of DNA in liquid matrices frozen on a liquid nitrogen-cooled sample stage. Several solvent systems have resulted in reproducible mass spectra of single-stranded DNA oligomers.
A genetic-based method applied in fuzzy modeling (2002)

The identification of a fuzzy system model consists of two major phases: structure identification and parameter identification. The aim of the paper is to determine the main aspects involved in developing a flexible method able to learn and optimize both the structure and the parameters of a fuzzy inference system (FIS) with applications in fuzzy modeling. We propose a special kind of GA with variable length genotypes. We tried to avoid the difficult problem of designing a recombination operator for parents of different sizes because in the natural environment we usually cannot find a correspondence for it.
Relationship between band gap and bond length alternation in organic conjugated polymers (1985)

We describe calculations of the evolution of the band gap as a function of geometry in conjugated polymers based on aromatic rings: polyparaphenylene, polypyrrole, polythiophene. Our results demonstrate that the gap decreases as a function of increasing quinoid character of the backbone and is thus not minimal in the case of zero bond length alternation, in contrast to the situation found in polyacetylene-like compounds. We stress the consequences of these results for the understanding of the effects of doping and for the design of new organic polymers with small gaps.
Management of the ig gene for haploid induction in maize (1992)

&mdash; The effect of the ig gene showed the same intensity at the haploid as at the diploid level. This was contrary to the results on the exceptional rate obtained elsewhere, and suggested that haploid manipulation should not be used as a routine procedure. At the diploid level, the genetic background of the ig gene has a strong effect in paternal haploid induction. In backcrosses of W23 ig as the initial source with recurrent inbred lines which were more or less related to the Golden Glow OP origin, pleiotropic effects differed according to the genetic background in the offspring. If male sterility observed at the ho- mozygous stage was still present, the other effects were completely lost from the initial cross with lines of the same origin (W25, CG3). On the other hand, they were maintained at a similar level in backcrosses with some non-related lines (F1254 for polyembryony). Due to its earliness the C0220 inbred line, in which the ig gene manipulation procedure is of interest, was shown to maintain a fairly good level of haploid induction in backcross and appears to be a promising background.
Elastic, piezoelectric, and dielectric properties of 0.58Pb(Mg1/3Nb2/3)O3-0.42PbTiO3 single crystal (2004)

The elastic, piezoelectric, and dielectric constants of 0.58Pb(Mg1/3Nb2/3)O3-0.42PbTiO3 (PMN-42%PT) were determined experimentally using combined resonance and ultrasonic methods. At room temperature the PMN-42%PT single crystal has tetragonal symmetry. The measured piezoelectric constant d33 is ∼260×10−12 C/N. The electromechanical coefficients k15, k31, k33, and kt are 0.80, 0.39, 0.78, and 0.62, respectively. From the measured material constants the orientational dependence of phase velocities and electromechanical coupling coefficients was calculated. The results showed the tetragonal crystal exhibits isotropy in the X-Y plane and k15, k33, and kt reach their maxima in [001].
Elementary Arithmetic Operations by Enzymes: A Model for Metabolic Pathway Based Computing (2006)

Physio-logical: A system of four enzymes, horseradish peroxidase, glucose dehydrogenase, glucose oxidase, and catalase, operate in parallel in the presence of NADH and NAD+ to yield AND and XOR gates (see picture). Glucose and H2O2 act as the inputs, and the absorbance that follows the production of gluconic acid or NADH provide the outputs of the AND and XOR gates, respectively. Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2002/2006/z503314_s.pdf or from the author. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Cameleon calcium indicator reports cytoplasmic calcium dynamics in Arabidopsis guard cells (1999)

Cytoplasmic free calcium ([Ca2+]cyt) acts as a stimulus-induced second messenger in plant cells and multiple signal transduction pathways regulate [Ca2+]cyt in stomatal guard cells. Measuring [Ca2+]cyt in guard cells has previously required loading of calcium-sensitive dyes using invasive and technically difficult micro-injection techniques. To circumvent these problems, we have constitutively expressed the pH-independent, green fluorescent protein-based calcium indicator yellow cameleon 2.1 in Arabidopsis thaliana (Miyawaki et al. 1999; Proc. Natl. Acad. Sci. USA 96, 2135-2140). This yellow cameleon calcium indicator was expressed in guard cells and accumulated predominantly in the cytoplasm. Fluorescence ratio imaging of yellow cameleon 2.1 allowed time-dependent measurements of [Ca2+]cyt in Arabidopsis guard cells. Application of extracellular calcium or the hormone abscisic acid (ABA) induced repetitive [Ca2+]cyt transients in guard cells. [Ca2+]cyt changes could be semi-quantitatively determined following correction of the calibration procedure for chloroplast autofluorescence. Extracellular calcium induced repetitive [Ca2+]cyt transients with peak values of up to approximately 1.5 microM, whereas ABA-induced [Ca2+]cyt transients had peak values up to approximately 0.6 microM. These values are similar to stimulus-induced [Ca2+]cyt changes previously reported in plant cells using ratiometric dyes or aequorin. In some guard cells perfused with low extracellular KCl concentrations, spontaneous calcium transients were observed. As yellow cameleon 2.1 was expressed in all guard cells, [Ca2+]cyt was measured independently in the two guard cells of single stomates for the first time. ABA-induced, calcium-induced or spontaneous [Ca2+]cyt increases were not necessarily synchronized in the two guard cells. Overall, these data demonstrate that that GFP-based cameleon calcium indicators are suitable to measure [Ca2+]cyt changes in guard cells and enable the pattern of [Ca2+]cyt dynamics to be measured with a high level of reproducibility in Arabidopsis cells. This technical advance in combination with cell biological and molecular genetic approaches will become an invaluable tool in the dissection of plant cell signal transduction pathways.
Excessive CpG island hypermethylation in cancer cell lines versus primary human malignancies (2001)

Cancer cell lines are widely used in many types of cancer research, including studies aimed at understanding DNA hypermethylation of gene promoters in cancer. Hypermethylation of promoters is capable of repressing the expression of tumor suppressor genes and may play a role in the development and/or progression of cancer. Although both primary malignancies and cancer cell lines exhibit this epigenetic phenomenon, there has been no direct comparison between them. In order to address this question, we have utilized restriction landmark genomic scanning to measure the hypermethylation phenotypes of cancer cell lines and compared these data with the same analysis performed on primary malignancies. In all cases, cancer cell lines exhibit significantly higher levels of CpG island hypermethylation than the primary malignancies they represent. Colon cancer cell lines are most similar to their respective tumors, with only a 5-fold increase in hypermethylation, while head and neck squamous cell carcinoma cell lines show a 93-fold increase in hypermethylation. Furthermore, >57% of the loci methylated in cell lines are never methylated in 114 primary malignancies studied. Seventy percent of loci hypermethylated in cell lines are hypermethylated in lines from more than one type of cancer. These data indicate that most CpG island hypermethylation observed in cancer cell lines is due to an intrinsic property of cell lines as opposed to the malignant tissue from which they originated.
The Rise of Azide—Alkyne 1,3‐Dipolar “Click” Cycloaddition and Its Application to Polymer Science and Surface Modification (2007)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
A fluorescence photographic photometric technique to assess stratum corneum turnover rate and barrier function in vivo (1982)

A photographic photometric method for objective measurement of fluorescence in skin is described. This method has been used to (a) improve the dansyl chloride method for determining stratum corneum turnover time by making assessments objective and quantitative, and (b) examine the barrier function of the stratum corneum by measuring the concentration of a fluorescent material at different levels within the stratum corneum at different times.
Coupling of gap plasmons in multi-wire waveguides (2009)

We investigate the coupling of gap plasmons in various configurations of neighboring metallic nanowires. Starting with the basic element defining a gap plasmon, consisting of two neighboring silver wires, we study the energy splitting and symmetry properties of hybridized plasmons resulting from the interaction of two wire pairs. The system is shown to display non-avoided crossings of hybridized modes, and it evolves at short distances towards a degenerate system consisting of four wires arranged in a square, where two new gap plasmons emerge from redshifted higher-energy modes. The gap modes of three neighboring wires are also described in a continuous transition from a coplanar configuration to an equilateral triangle arrangement. The interaction between wire pairs is shown to be weak enough to prevent efficient transfer of plasmon signal from a pair to the other one, which is beneficial to avoid crosstalking, but not to produce waveguide couplers. The coupling is significantly increased by placing a wire of rectangular cross section in between the wire pairs, thus allowing us to achieve large plasmon-signal transfers within propagation distances below the attenuation length. Our results can find application in the design of signal-processing devices based upon gap plasmons.
ICOS+PD-1+CXCR3+ T follicular helper cells contribute to the generation of high-avidity antibodies following influenza vaccination (2016)

The immune mechanism leading to the generation of protective antibody responses following influenza trivalent inactivated vaccine (TIV) vaccinations remains largely uncharacterized. We recently reported that TIV vaccination induced a transient increase of circulating ICOS(+)PD-1(+)CXCR3(+) T follicular helper (cTfh) cells in blood, which positively correlated with the induction of protective antibody responses measured at day 28. However, whether and how these T cells directly contribute to antibody response remains unclear. In this study, we analyzed the changes after TIV vaccination in the amount and the avidity of the polyclonal antibodies specific for the HA1 subunit of the pandemic H1N1 virus, and analyzed the correlation with the increase of ICOS(+)PD-1(+)CXCR3(+) cTfh cells. We found that both the amount and the avidity of specific antibodies rapidly increased during the first 7 days after TIV. Importantly, the increase of ICOS(+)PD-1(+)CXCR3(+) cTfh cells strongly correlated with the increase in the avidity of antibodies, particularly in subjects who did not have high affinity antibodies at baseline. We propose that ICOS(+)PD-1(+)CXCR3(+) Tfh cells directly contribute to the generation of high-avidity antibodies after TIV vaccinations by selectively interacting with high affinity B cells at extrafollicular sites.
Rab 7: an important regulator of late endocytic membrane traffic. (1995)

Rab5 and rab7 proteins belong to a superfamily of small molecular weight GTPases known to be associated with early and late endosomes, respectively. The rab5 protein plays an important regulatory role in early endocytosis, yet the function of rab7 protein was previously uncharacterized. This question was addressed by comparing the kinetics of vesicular stomatitis virus (VSV) G protein internalization in baby hamster kidney cells overexpressing wild-type or dominant negative mutant forms of the rab7 protein (rab7N125I and rab7T22N). Overexpression of wild-type rab7 protein allowed normal transport to late endosomes (mannose 6-phosphate receptor positive), while the rab7N125I mutant caused the VSV G protein to accumulate specifically in early (transferrin receptor positive) endosomes. Horseradish peroxidase and paramyxovirus SV5 hemagglutinin-neuraminidase (HN) were used in quantitative biochemical assays to further demonstrate that rab7 function was not required for early internalization events, but was crucial in downstream degradative events. The characteristic cleavage of SV5 HN in the late endosome distinguishes internalization from transport to later stages of the endocytic pathway. Mutant rab7N125I or rab7T22N proteins had no effect on the internalization of either horseradish peroxidase or SV5 HN protein. In contrast, the mutant proteins markedly inhibited the subsequent cleavage of the SV5 HN protein. Taken together, these data support a key role for rab7, downstream of rab5, in regulating membrane transport leading from early to late endosomes. We compare our findings to those obtained for the yeast homologues Ypt51p, Ypt52p, Ypt53p, and Ypt7p.