gebhart/patrepeval huggingface dataset:
Re-sequencing Expands Our Understanding of the Phenotypic Impact of Variants at GWAS Loci (2014)

Genome-wide association studies (GWAS) have identified >500 common variants associated with quantitative metabolic traits, but in aggregate such variants explain at most 20-30% of the heritable component of population variation in these traits. To further investigate the impact of genotypic variation on metabolic traits, we conducted re-sequencing studies in >6,000 members of a Finnish population cohort (The Northern Finland Birth Cohort of 1966 [NFBC]) and a type 2 diabetes case-control sample (The Finland-United States Investigation of NIDDM Genetics [FUSION] study). By sequencing the coding sequence and 5' and 3' untranslated regions of 78 genes at 17 GWAS loci associated with one or more of six metabolic traits (serum levels of fasting HDL-C, LDL-C, total cholesterol, triglycerides, plasma glucose, and insulin), and conducting both single-variant and gene-level association tests, we obtained a more complete understanding of phenotype-genotype associations at eight of these loci. At all eight of these loci, the identification of new associations provides significant evidence for multiple genetic signals to one or more phenotypes, and at two loci, in the genes ABCA1 and CETP, we found significant gene-level evidence of association to non-synonymous variants with MAF<1%. Additionally, two potentially deleterious variants that demonstrated significant associations (rs138726309, a missense variant in G6PC2, and rs28933094, a missense variant in LIPC) were considerably more common in these Finnish samples than in European reference populations, supporting our prior hypothesis that deleterious variants could attain high frequencies in this isolated population, likely due to the effects of population bottlenecks. Our results highlight the value of large, well-phenotyped samples for rare-variant association analysis, and the challenge of evaluating the phenotypic impact of such variants.
Supplementary Figures from Identification of Targetable FGFR Gene Fusions in Diverse Cancers (2023)

&lt;p&gt;Supplementary Figures - PDF file 639K, Supplementary Figures S1-S9 show the phenotypic effects and signaling pathways of FGFR fusions in vitro and in vivo&lt;/p&gt;
A Mild Method for the Formation and in Situ Reaction of Imidoyl Chlorides:  Conversion of Pyridine-1-oxides to 2-Aminopyridine Amides (2002)

[reaction: see text] A mild, practical, one-pot method for the generation of imidoyl chlorides and their subsequent in situ reaction with pyridine-1-oxides is described. The imidoyl chlorides were formed from the reaction of secondary amides with a stoichiometric amount of oxalyl chloride and 2,6-lutidine in CH(2)Cl(2) at 0 degrees C. Upon warming of the reaction mixture to room temperature in the presence of pyridine-1-oxides, a rapid conversion to 2-aminopyridine amides was observed in moderate to excellent isolated yields.
The structure of the HeI2 van der Waals molecule (1978)

The rotational structure of the fluorescence excitation spectrum of the B (v′=10) ←X (v″=0) transition of the van der Waals molecule HeI2 has been measured and analyzed. The analysis indicates that the molecule has a nonlinear equilibrium structure with R′=4.79±0.22 Å and R″=4.47±0.13 Å, where R is the perpendicular distance from the helium atom to a line drawn through the iodine atoms.
Dynamic power gating with quality guarantees (2009)

Power gating is usually driven by a predictive control, and frequent mispredictions can counter-productively lead to a large increase in energy consumption. This energy vulnerability could be exploited by malicious applications such as a power virus, or it may be exposed by regular applications containing repetitive mispredictions patterns. We propose counteracting this vulnerability by using a guard mechanism to prevent power overruns.
Using Trust and Anonymity to Expand the Use of Anonymizing Systems that Improve Security Across Organizations and Nations (2015)

To mitigate risks inherent in sharing sensitive cyber-security information, recent research has examined anonymizing systems (ANS) that hide the identities of participants and decouple data from their originators. ANS are particularly compelling as a potential support to cyber-security information sharing because the cost of implementation is relatively low, and the more organizations and nations that participate, the more everyone benefits. Although such systems are promising to both developing and mature cyber-infrastructures, they still have not been widely adopted for use in sharing cyber-security information. Relatively little prior research has investigated the perception and adoption of these systems, despite their potential value for organizations and nations in supporting the battle against cyber-crime.Given these opportunities, this study tries to better understand the factors that foster adoption of ANS. Accordingly, we present a theoretical model intended to explain the trust process involved in user adoption of anonymizing systems. We theorize that users’ beliefs regarding trust in the information provided by the system and the risks associated with using the system, as well as beliefs in the system’s anonymizing capability, will lead to greater levels of adoption. Further, perceptions of system quality are theorized to contribute to user trusting beliefs. The results of a free-simulation experiment largely validate the proposed model. These results should help inform the next generation of ANS development and deployment.
Symmetry breakage in the development of one-armed gonads in nematodes (1996)

Whereas the hermaphrodite gonad of Caenorhabditis elegans has two symmetric arms (didelphy), the female/hermaphrodite gonad of many nematode species features a single anterior arm (monodelphy). We examined how gonadal cell lineages and intercellular signalling evolve to generate these diverse structures. In C. elegans, the two arms develop symmetrically from two somatic precursor cells, Z1 (anterior) and Z4 (posterior). Each first gives rise to one distal tip cell (which promotes arm growth and germ line proliferation), two ovary precursors and three uterine precursors in the center of the developing gonad. In monodelphic species, Z1 and Z4 have different fates. The first visible asymmetry between them is in the relative timing of their divisions, followed by asymmetric cell movements. The putative posterior distal tip cell is then eliminated in all but one species by programmed cell death. In some species the posterior ovary precursors form a small vestigial posterior arm, the post-vulval sac; in other species, they stay undivided, or die. In Cephalobus sp. PS1197, the specific fate of Z4 progeny is induced by Z1 (or its daughters). In the uterus in C. elegans, symmetric lateral signalling between Z1.ppp and Z4.aaa renders them equally likely to become the anchor cell, which links the uterus to the vulva. In the different monodelphic species, anchor cell specification is biased, or fully fixed, to a descendant of either Z1 or Z4. Replacement regulation upon anchor cell ablation is conserved in some species, but lost in others, leading to a mosaic-type development. Differentiation between Z1 and Z4 is thus manifested at this later stage in the breakage of symmetry of cell interactions in the ventral uterus.
Triple Arthrodesis through a Single Lateral Approach: A Cadaveric Experiment (1992)

Using a single lateral approach, triple arthrodesis was performed on six cadaveric feet. An attempt was made to obliterate the talocalcaneal, talonavicular, and calcaneocuboid joints. The limbs were subsequently disarticulated to allow for an inspection of the talonavicular, talocalcaneal, and calcaneocuboid joints. An estimate of cartilage and subchondral bone removed from each articular surface was made by a single observer (J.V.B.) by direct visual inspection. Results were as follows: calcaneocuboid joint, 90% of cartilage removed; talocalcaneal joint, 80% of cartilage removed; talonavicular joint, 38% of cartilage removed. Failures at the talonavicular joint were attributed to a poor appreciation of the anatomy of the talar head and poor observation. Complications involved in obliteration of the talonavicular joint from a single lateral approach included: inadvertent division of the talar neck; inadvertent division of the talar head; removal of excessive bone stock; medial skin punctures; and creation of an iatrogenic cut through the talar dome. Therefore, a triple arthrodesis through a single lateral approach, as described by Ryerson, Hoke, and Campbell, cannot be recommended. The talonavicular joint should be approached through an auxiliary medial incision, as recommended by Cracchiolo. This paper documents the experience of a beginner with this operation, and demonstrates the value of using the anatomy laboratory.
Improving the numerical integration solution of satellite orbits in the presence of solar radiation pressure using modified back differences (1991)

The method of modified back differences, a technique that significantly reduces the numerical integration errors associated with crossing shadow boundaries using a fixed-mesh multistep integrator without a significant increase in computer run time, is presented. While Hubbard's integral approach can produce significant improvements to the trajectory solution, the interpolation method provides the best overall results. It is demonstrated that iterating on the point mass term correction is also important for achieving the best overall results. It is also shown that the method of modified back differences can be implemented with only a small increase in execution time.
Detection and isolation of plant‐associated bacteria scavenging atmospheric molecular hydrogen (2015)

High-affinity hydrogen (H2 )-oxidizing bacteria possessing group 5 [NiFe]-hydrogenase genes are important contributors to atmospheric H2 uptake in soil environments. Although previous studies reported the occurrence of a significant H2 uptake activity in vegetation, there has been no report on the identification and diversity of the responsible microorganisms. Here, we show the existence of plant-associated bacteria with the ability to consume atmospheric H2 that may be a potential energy source required for their persistence in plants. Detection of the gene hhyL - encoding the large subunit of group 5 [NiFe]-hydrogenase - in plant tissues showed that plant-associated high-affinity H2 -oxidizing bacteria are widely distributed in herbaceous plants. Among a collection of 145 endophytic isolates, seven Streptomyces strains were shown to possess hhyL gene and exhibit high- or intermediate-affinity H2 uptake activity. Inoculation of Arabidopsis thaliana (thale cress) and Oryza sativa (rice) seedlings with selected isolates resulted in an internalization of the bacteria in plant tissues. H2 uptake activity per bacterial cells was comparable between plant and soil, demonstrating that both environments are favourable for the H2 uptake activity of streptomycetes. This study first demonstrated the occurrence of plant-associated high-affinity H2 -oxidizing bacteria and proposed their potential contribution as atmospheric H2 sink.
Novel Fluoro-carbon Functional Monomer for Dental Bonding (2013)

Among several functional monomers, 10-methacryloxydecyl dihydrogen phosphate (10-MDP) bonded most effectively to hydroxyapatite (HAp). However, more hydrolysis-resistant functional monomers are needed to improve bond durability. Here, we investigated the adhesive potential of the novel fluoro-carbon functional monomer 6-methacryloxy-2,2,3,3,4,4,5,5-octafluorohexyl dihydrogen phosphate (MF8P; Kuraray Noritake Dental Inc., Tokyo, Japan) by studying its molecular interaction with powder HAp using solid-state nuclear magnetic resonance ((1)H MAS NMR) and with dentin using x-ray diffraction (XRD) and by characterizing its interface ultrastructure at dentin using transmission electron microscopy (TEM). We further determined the dissolution rate of the MF8P_Ca salt, the hydrophobicity of MF8P, and the bond strength of an experimental MF8P-based adhesive to dentin. NMR confirmed chemical adsorption of MF8P onto HAp. XRD and TEM revealed MF8P_Ca salt formation and nano-layering at dentin. The MF8P_Ca salt was as stable as that of 10-MDP; MF8P was as hydrophobic as 10-MDP; a significantly higher bond strength was recorded for MF8P than for 10-MDP. In conclusion, MF8P chemically bonded to HAp. Despite its shorter size, MF8P possesses characteristics similar to those of 10-MDP, most likely to be associated with the strong chemical bond between fluorine and carbon. Since favorable bond strength to dentin was recorded, MF8P can be considered a good candidate functional monomer for bonding.
Cellular Dynamics and Genomic Identity of Centromeres in Cereal Blast Fungus (2019)

Precise kinetochore-microtubule interactions ensure faithful chromosome segregation in eukaryotes. Centromeres, identified as scaffolding sites for kinetochore assembly, are among the most rapidly evolving chromosomal loci in terms of the DNA sequence and length and organization of intrinsic elements. Neither the centromere structure nor the kinetochore dynamics is well studied in plant-pathogenic fungi. Here, we sought to understand the process of chromosome segregation in the rice blast fungus <i>Magnaporthe oryzae</i> High-resolution imaging of green fluorescent protein (GFP)-tagged inner kinetochore proteins CenpA and CenpC revealed unusual albeit transient declustering of centromeres just before anaphase separation of chromosomes in <i>M. oryzae</i> Strikingly, the declustered centromeres positioned randomly at the spindle midzone without an apparent metaphase plate <i>per se</i> Using CenpA chromatin immunoprecipitation followed by deep sequencing, all seven centromeres in <i>M. oryzae</i> were found to be regional, spanning 57-kb to 109-kb transcriptionally poor regions. Highly AT-rich and heavily methylated DNA sequences were the only common defining features of all the centromeres in rice blast. Lack of centromere-specific DNA sequence motifs or repetitive elements suggests an epigenetic specification of centromere function in <i>M. oryzae</i> PacBio genome assemblies and synteny analyses facilitated comparison of the centromeric/pericentromeric regions in distinct isolates of rice blast and wheat blast and in <i>Magnaporthiopsis poae</i> Overall, this study revealed unusual centromere dynamics and precisely identified the centromere loci in the top model fungal pathogens that belong to <i>Magnaporthales</i> and cause severe losses in the global production of food crops and turf grasses.<b>IMPORTANCE</b><i>Magnaporthe oryzae</i> is an important fungal pathogen that causes a loss of 10% to 30% of the annual rice crop due to the devastating blast disease. In most organisms, kinetochores are clustered together or arranged at the metaphase plate to facilitate synchronized anaphase separation of sister chromatids in mitosis. In this study, we showed that the initially clustered kinetochores separate and position randomly prior to anaphase in <i>M. oryzae</i> Centromeres in <i>M. oryzae</i> occupy large genomic regions and form on AT-rich DNA without any common sequence motifs. Overall, this study identified atypical kinetochore dynamics and mapped functional centromeres in <i>M. oryzae</i> to define the roles of centromeric and pericentric boundaries in kinetochore assembly on epigenetically specified centromere loci. This study should pave the way for further understanding of the contribution of heterochromatin in genome stability and virulence of the blast fungus and its related species of high economic importance.
Enabling Technology for 9.5-dB SNR Enhancement Utilizing Four-Wave Mixing Between a Conjugate Pair of Angle Modulation for Analog Radio-over-Fiber Links (2021)

We demonstrate a new application of four-wave mixing which enhances the SNR of angle-modulated RoF signals by 9.5 dB. We experimentally confirmed that the method produced an 8.8-dB enhancement and demonstrated a 400-MHz 1024-QAM transmission.
Cloning and functional characterization of extracellular Ca2+-sensing receptors from parathyroid and kidney (1995)

Parathyroid cells recognize and respond to (i.e., "sense") minute perturbations in the extracellular ionized calcium concentration (Ca2+o), but the mechanisms underlying this process have remained obscure. Recently, we employed expression cloning in Xenopus laevis oocytes to isolate a cDNA coding for a Ca2+o-sensing receptor from bovine parathyroid. Like the native receptor, the cloned Ca2+o-sensing receptor stimulates phospholipase C (PLC) in a G-protein-dependent manner with a nearly identical pharmacological profile. Its deduced amino acid sequence confirms that it is a member of the superfamily of G-protein-coupled receptors (GPR). Transcripts for the receptor are expressed in parathyroid and other tissues that sense Ca2+o (viz., kidney and thyroidal C-cells) as well as those that have no known role in extracellular Ca2+ homeostasis, such as the brain. The availability of the cDNA clone for the Ca2+o-sensing receptor made it possible to test the hypothesis that mutations in the gene encoding the human homolog of the receptor cause inherited disorders of mineral ion metabolism. Familial hypocalciuric hypercalcemia (FHH) and neonatal severe hyperparathyroidism (NSHPT) are, in fact, caused by mutations that reduce the activity of the receptor when they are present in the heterozygous and homozygous states, respectively. In contrast, we have subsequently discovered a family in which a form of autosomal dominant hypocalcemia results from an activating mutation in the receptor gene. The Ca2+-sensing receptor, therefore, permits Ca2+o to play a "hormonelike" role as an extracellular first messenger in addition to its well described role as an important intracellular second messenger.
Multiwell Thermal Interaction: Field-Data Validation of Transient Model for Closely Spaced Wells (2013)

Summary Wellbore-temperature logs and associated field-history data from a high-pressure/high-temperature (HP/HT) condensate North Sea platform are presented that validate the accuracy of a transient model of the multiwell thermal interaction (MWTI). The model is an updated version of previous work by McSpadden and Coker (2010) that simulates transient thermal interaction or "cross heating" between closely spaced wells of a template. As discussed in the preceding work, the MWTI alters final wellbore temperatures as well as formation temperatures in the interwell zone and also farther out from the well template. The multiwell thermal model is shown to converge closely in very characteristic fashion to two different logged and measured temperature profiles at a vertical depth range of more than 3,000 ft. The empirical data, including field history, represent a unique opportunity to study and understand this important topic. Before this current work, the authors’ experience found the industry discussion of the MWTI or "cross heating" to be largely anecdotal. Model validation against field data is necessary to achieve a full understanding of the physical system and to provide confidence in the predictive capability. The modeling of wellbore and formation temperatures for closely spaced wells has not been widely examined in the industry literature, as observed by Bellarby (2009). The current work presents an improved methodology on the basis of standard-industry techniques. The method uses standard industry thermal/hydraulic modeling software for a single well and a fully transient finite-difference model for the formation in a loosely coupled, iterative analysis. The iteration scheme is achieved by the coupling of the standard analytical solution for the isolated single-well temperature scenario with the solution in the formation for the cross-heating scenario. The effect of the MWTI is important for closely spaced wells such as offshore platforms or subsea and Arctic developments. The multiwell disturbance on formation and wellbore temperatures may affect well design, facilities planning, and operations. For example, given nominal flowing wellhead temperatures (FWHTs) approaching 350°F for HP/HT platform developments, even small temperature increases may have a critical impact on the design and layout of surface receiving systems. Annular-pressure buildup (APB), wellhead movement, tubular-stress design, cement-slurry design, subsidence/compaction effects, and facilities health and safety issues can all be affected. If the MWTI is not taken into account, then load events such as APB, wellhead movement, and thermally induced stresses may be underestimated. Concurrent and batch-drilling operations, including cementation, will also be affected.
Screening potential inhibitors against Alzheimer's amyloidosis using electrospray ionization mass spectrometry (2008)

Alzheimer's disease (AD) is associated with neurodegeneration, premature death and has a major impact on health along with economical ramifications in Western world. The prevailing hypotheses regarding the cause of AD have centered on the amyloid beta protein (Aβ)-containing senile plaques. In light of the suggested link between oxidative stress and Aβ's aggregation, the use of antioxidants as a therapeutic regime for protection against the risk of this disease has to be explored. The binding of Aβ with endogenous or plant-derived bioactive antioxidants via the formation of noncovalent complexes has been studied by electrospray ionization (ESI) mass spectrometry (MS). The stability and specificity of the complexes has been examined under several experimental parameters, while the topology of the interacting species has been revealed by proteolytic mapping, in conjunction with ESI Fourier Transform Ion Cyclotron (FTICR) MS analysis. The ligands that bind to Aβ could be used as potential aggregation inhibitors and serve as lead compounds for the synthesis of anti-amyloidogenic agents against AD.