gebhart/patrepeval huggingface dataset:
Archaeal DNA Polymerase D but Not DNA Polymerase B Is Required for Genome Replication in Thermococcus kodakarensis (2013)

Three evolutionarily distinct families of replicative DNA polymerases, designated polymerase B (Pol B), Pol C, and Pol D, have been identified. Members of the Pol B family are present in all three domains of life, whereas Pol C exists only in Bacteria and Pol D exists only in Archaea. Pol B enzymes replicate eukaryotic chromosomal DNA, and as members of the Pol B family are present in all Archaea, it has been assumed that Pol B enzymes also replicate archaeal genomes. Here we report the construction of Thermococcus kodakarensis strains with mutations that delete or inactivate key functions of Pol B. T. kodakarensis strains lacking Pol B had no detectable loss in viability and no growth defects or changes in spontaneous mutation frequency but had increased sensitivity to UV irradiation. In contrast, we were unable to introduce mutations that inactivated either of the genes encoding the two subunits of Pol D. The results reported establish that Pol D is sufficient for viability and genome replication in T. kodakarensis and argue that Pol D rather than Pol B is likely the replicative DNA polymerase in this archaeon. The majority of Archaea contain Pol D, and, as discussed, if Pol D is the predominant replicative polymerase in Archaea, this profoundly impacts hypotheses for the origin(s), evolution, and distribution of the different DNA replication enzymes and systems now employed in the three domains of life.
Neue Synthese und Molekölstruktur des Pyren‐Isomers Dicyclohepta[cd,gh]pentalen (Azuleno[2,1,8‐ija]azulen) (1984)

Der planare Bau der Titelverbindung 1 konnte durch Röntgen‐Strukturanalyse bewiesen werden. Die Kürze der zentralen Bindung (1.35 Å) legt ein großes Gewicht der Resonanzstruktur B nahe; 1 kann also als ein durch die CC‐Brücke gestörtes [14]Annulen aufgefaßt werden. — Entscheidender Reaktionsschritt bei der Synthese ist eine neuartige Ramberg‐Bäcklund‐analoge Umlagerung. magnified image
Fhit Delocalizes Annexin A4 from Plasma Membrane to Cytosol and Sensitizes Lung Cancer Cells to Paclitaxel (2013)

Fhit protein is lost or reduced in a large fraction of human tumors, and its restoration triggers apoptosis and suppresses tumor formation or progression in preclinical models. Here, we describe the identification of candidate Fhit-interacting proteins with cytosolic and plasma membrane localization. Among these, Annexin 4 (ANXA4) was validated by co-immunoprecipitation and confocal microscopy as a partner of this novel Fhit protein complex. Here we report that overexpression of Fhit prevents Annexin A4 translocation from cytosol to plasma membrane in A549 lung cancer cells treated with paclitaxel. Moreover, paclitaxel administration in combination with AdFHIT acts synergistically to increase the apoptotic rate of tumor cells both in vitro and in vivo experiments.
Quantum dot based nanosensors designed for proteolytic monitoring (2006)

We have previously assembled QD-based fluorescence resonance energy transfer (FRET) sensors specific for the sugar nutrient maltose and the explosive TNT. These sensors utilize several inherent benefits of QDs as FRET donors. In this report, we show that QD-FRET based sensors can also function in the monitoring of proteolytic enzyme activity. We utilize a QD with multiple dye-labeled proteins attached to the surface as a substrate for a prototypical protease. We then demonstrate how this strategy can be extended to detect protease activity by utilizing a dye-labeled peptide attached to the QD as a proteolytic substrate. Self-assembly of the peptide-dye on the QD brings the dye in close proximity to the QD and result in efficient FRET. Addition of a proteolytic enzyme that specifically recognizes and cleaves the peptide alters the FRET signature of the sensor in a concentration-dependent manner. Both qualitative and quantitative data can be derived from these sensors. The potential benefits of this type of QD sensing strategy are discussed.
Use of a priori knowledge of vocabulary for real time discrete utterance recognition (2005)

Performance degradation of isolated word recognition systems on vocabularies with acoustically similar words is a well known problem. In many cases, vocabularies can be designed to eliminate this confusability. However, the English alphabet combined with digits is a fixed vocabulary which cannot be easily modified to be less confusable. We show how a priori phonetic knowledge of the alpha-digits vocabulary can be used during template generation to reduce error rate. Unlike methods proposed by Lamel and Zue or Rabiner and Wilpon, our technique requires only a single pass for recognition. Thus it is usable in a real time system. The alpha-digits vocabulary is partitioned into subclasses of words with common vowel phonemes, or in some cases allophones. Each subclass consists of words which differ only in the starting or final consonants. Templates are created so the common vowel in each subclass has one representation. For words in the same subclass, the match from the dynamic programming score reflects only initial or final consonant differences. Template storage space is reduced because the vowel portion of each template in the subclass is stored only once.
Longitudinal Development of Brain Iron Is Linked to Cognition in Youth (2020)

Brain iron is vital to multiple aspects of brain function, including oxidative metabolism, myelination, and neurotransmitter synthesis. Atypical iron concentration in the basal ganglia is associated with neurodegenerative disorders in aging and cognitive deficits. However, the normative development of brain iron concentration in adolescence and its relationship to cognition are less well understood. Here, we address this gap in a longitudinal sample of 922 humans aged 8-26 years at the first visit (M = 15.1, SD = 3.72; 336 males, 486 females) with up to four multiecho T2* scans each. Using this sample of 1236 imaging sessions, we assessed the longitudinal developmental trajectories of tissue iron in the basal ganglia. We quantified tissue iron concentration using R2* relaxometry within four basal ganglia regions, including the caudate, putamen, nucleus accumbens, and globus pallidus. The longitudinal development of R2* was modeled using generalized additive mixed models (GAMMs) with splines to capture linear and nonlinear developmental processes. We observed significant increases in R2* across all regions, with the greatest and most prolonged increases occurring in the globus pallidus and putamen. Further, we found that the developmental trajectory of R2* in the putamen is significantly related to individual differences in cognitive ability, such that greater cognitive ability is increasingly associated with greater iron concentration through late adolescence and young-adulthood. Together, our results suggest a prolonged period of basal ganglia iron enrichment that extends into the mid-twenties, with diminished iron concentration associated with poorer cognitive ability during late adolescence.<b>SIGNIFICANCE STATEMENT</b> Brain tissue iron is essential to healthy brain function. Atypical basal ganglia tissue iron levels have been linked to impaired cognition in iron deficient children and adults with neurodegenerative disorders. However, the normative developmental trajectory of basal ganglia iron concentration during adolescence and its association with cognition are less well understood. In the largest study of tissue iron development yet reported, we characterize the developmental trajectory of tissue iron concentration across the basal ganglia during adolescence and provide evidence that diminished iron content is associated with poorer cognitive performance even in healthy youth. These results highlight the transition from adolescence to adulthood as a period of dynamic maturation of tissue iron concentration in the basal ganglia.
Recruited macrophages elicit atrial fibrillation (2023)

Atrial fibrillation disrupts contraction of the atria, leading to stroke and heart failure. We deciphered how immune and stromal cells contribute to atrial fibrillation. Single-cell transcriptomes from human atria documented inflammatory monocyte and <i>SPP1</i><sup>+</sup> macrophage expansion in atrial fibrillation. Combining hypertension, obesity, and mitral valve regurgitation (HOMER) in mice elicited enlarged, fibrosed, and fibrillation-prone atria. Single-cell transcriptomes from HOMER mouse atria recapitulated cell composition and transcriptome changes observed in patients. Inhibiting monocyte migration reduced arrhythmia in <i>Ccr2</i><sup>-∕-</sup> HOMER mice. Cell-cell interaction analysis identified SPP1 as a pleiotropic signal that promotes atrial fibrillation through cross-talk with local immune and stromal cells. Deleting <i>Spp1</i> reduced atrial fibrillation in HOMER mice. These results identify SPP1<sup>+</sup> macrophages as targets for immunotherapy in atrial fibrillation.
Effect of bile on the oral absorption of halofantrine in polyethylene glycol 400 and polysorbate 80 formulations dosed to bile duct cannulated rats (2011)

The addition of PS 80 to the formulation increased its solubilising power upon dilution and may have inhibited precipitation and substituted the absence of bile above a certain level. Adjusting the level of surfactant in drug formulations could therefore be used to minimise variability in the bioavailability from co-solvent systems based upon differences in bile concentration between individuals.
Effect of dislocations on electron mobility in AlGaN/GaN and AlGaN/AlN/GaN heterostructures (2012)

AlxGa1−xN/GaN (x = 0.06, 0.12, 0.24) and AlGaN/AlN/GaN heterostructures were grown on 6 H-SiC, GaN-on-sapphire, and free-standing GaN, resulting in heterostructures with threading dislocation densities of ∼2 × 1010, ∼5 × 108, and ∼5 × 107 cm−2, respectively. All growths were performed under Ga-rich conditions by plasma-assisted molecular beam epitaxy. Dominant scattering mechanisms with variations in threading dislocation density and sheet concentration were indicated through temperature-dependent Hall measurements. The inclusion of an AlN interlayer was also considered. Dislocation scattering contributed to reduced mobility in these heterostructures, especially when sheet concentration was low or when an AlN interlayer was present.
Supp. Table S2 from Genetic Mechanisms of Immune Evasion in Colorectal Cancer (2023)

&lt;p&gt;Supplementary Table S2: Somatic mutations&lt;/p&gt;
Peracylation of Nucleosides with Methionine: Foundation for a Method To Detect Carcinogen Adducts (1994)

We report the chemical foundation for a new method to detect carcinogen-DNA adducts, which we have designated adduct detection by acylation with methionine (ADAM). The method is based on reaction of DNA adducts with a protected methionine derivative, (tert-butoxycarbonyl)-L-methionine N-hydroxysuccinimidyl ester (TMB-NHS). Acylation of 2'-deoxyguanosine (dGuo), used as a prototypical deoxynucleoside, and N-(deoxyguanosin-8-yl)-4-aminobiphenyl (dGuo-8-ABP), the major DNA adduct formed after in vivo exposure to 4-aminobiphenyl, a known human carcinogen, with TBM-NHS was optimized, and products were characterized by 3H radioactivity, UV absorbance, mass spectrometry, and 1H and 13C NMR. Derivatives acylated on hydroxyl (5' or 3') and/or amine (N2) groups were unambiguously determined to be mono-, bis-, and tris-TBM-acylated nucleosides. Under optimal acylation conditions [TBM-NHS (> or = 4 x 10(5) molar equivalents), pyridine (50 microL), THF (50 microL), and diisopropylcarbodiimide (DIC) (1 microL) and incubation for 2 h at 37 degrees C], the efficiency of acylation for picomole or smaller quantities of dGuo-8-ABP exceeded 95%, with the tris-TMB-acylated nucleoside representing the major product (88%). A linear correlation was obtained between the amount of [3H]dGuo-8-ABP introduced into the reaction and the total amount of TBM-acylated products formed. These results support the validity of this strategy for adaptation as an analytical method for the detection of low levels of DNA adducts through the use of (tert-butoxycarbonyl)-L-[35S]-methionine N-hydroxysuccinimidyl ester.
Remote-LFA Node Protection and Manageability (2017)

The loop-free alternates (LFAs) computed following the current remote-
LFA specification guarantees only link protection. The resulting
remote-LFA next hops (also called PQ-nodes) may not guarantee node
protection for all destinations being protected by it. This document
describes an extension to the remote-loop-free-based IP fast reroute
mechanisms that specifies procedures for determining whether or not a
given PQ-node provides node protection for a specific destination. The
document also shows how the same procedure can be utilized for the
collection of complete characteristics for alternate paths. Knowledge
about the characteristics of all alternate paths is a precursor to
applying the operator-defined policy for eliminating paths not fitting
the constraints.
Desmoplastic stroma restricts T cell extravasation and mediates immune exclusion and immunosuppression in solid tumors (2023)

The desmoplastic stroma in solid tumors presents a formidable challenge to immunotherapies that rely on endogenous or adoptively transferred T cells, however, the mechanisms are poorly understood. To define mechanisms involved, we treat established desmoplastic pancreatic tumors with CAR T cells directed to fibroblast activation protein (FAP), an enzyme highly overexpressed on a subset of cancer-associated fibroblasts (CAFs). Depletion of FAP<sup>+</sup>CAFs results in loss of the structural integrity of desmoplastic matrix. This renders these highly treatment-resistant cancers susceptible to subsequent treatment with a tumor antigen (mesothelin)-targeted CAR and to anti-PD1 antibody therapy. Mechanisms include overcoming stroma-dependent restriction of T cell extravasation and/or perivascular invasion, reversing immune exclusion, relieving T cell suppression, and altering the immune landscape by reducing myeloid cell accumulation and increasing endogenous CD8<sup>+</sup> T cell and NK cell infiltration. These data provide strong rationale for combining tumor stroma- and malignant cell-targeted therapies to be tested in clinical trials.
Dual-element off-axis eyeglass-based display (2006)

We describe the optical system design and analysis of a wearable dual-element off-axis display based on a magnifier form that supports an 8mm exit pupil and a 20 degree diagonal full field of view. © 2006 SPIE-OSA.
Data from Effect of Small-Molecule Modification on Single-Cell Pharmacokinetics of PARP Inhibitors (2023)

&lt;div&gt;Abstract&lt;p&gt;The heterogeneous delivery of drugs in tumors is an established process contributing to variability in treatment outcome. Despite the general acceptance of variable delivery, the study of the underlying causes is challenging, given the complex tumor microenvironment including intra- and intertumor heterogeneity. The difficulty in studying this distribution is even more significant for small-molecule drugs where radiolabeled compounds or mass spectrometry detection lack the spatial and temporal resolution required to quantify the kinetics of drug distribution &lt;i&gt;in vivo&lt;/i&gt;. In this work, we take advantage of the synthesis of fluorescent drug conjugates that retain their target binding but are designed with different physiochemical and thus pharmacokinetic properties. Using these probes, we followed the drug distribution in cell culture and tumor xenografts with temporal resolution of seconds and subcellular spatial resolution. These measurements, including &lt;i&gt;in vivo&lt;/i&gt; permeability of small-molecule drugs, can be used directly in predictive pharmacokinetic models for the design of therapeutics and companion imaging agents as demonstrated by a finite element model. &lt;i&gt;Mol Cancer Ther; 13(4); 986–95. ©2014 AACR&lt;/i&gt;.&lt;/p&gt;&lt;/div&gt;
Advantages of Soft versus Hard Constraints in Self-Modeling Curve Resolution Problems. Penalty Alternating Least Squares (P-ALS) Extension to Multi-Way Problems (2008)

An extension to the penalty alternating least squares (P-ALS) method, called multi-way penalty alternating least squares (NWAY P-ALS), is presented. Optionally, hard constraints (no deviation from predefined constraints) or soft constraints (small deviations from predefined constraints) were applied through the application of a row-wise penalty least squares function. NWAY P-ALS was applied to the multi-batch near-infrared (NIR) data acquired from the base catalyzed esterification reaction of acetic anhydride in order to resolve the concentration and spectral profiles of 1-butanol with the reaction constituents. Application of the NWAY P-ALS approach resulted in the reduction of the number of active constraints at the solution point, while the batch column-wise augmentation allowed hard constraints in the spectral profiles and resolved rank deficiency problems of the measurement matrix. The results were compared with the multi-way multivariate curve resolution (MCR)-ALS results using hard and soft constraints to determine whether any advantages had been gained through using the weighted least squares function of NWAY P-ALS over the MCR-ALS resolution.
Method to measure orientation of discontinuous fiber embedded in the polymer matrix from computerized tomography scan data (2015)

Usage of discontinuous glass fibers in injection- and compression-molded resin components is rapidly increasing to improve their mechanical properties. Since added fiber contributes to more strength along the fiber direction compared with transverse direction, the mechanical properties of such components strongly depend on the fiber orientation. Therefore, it is important to estimate the fiber orientation distribution in such materials. In this article, we are presenting a recently developed method to estimate fiber orientation using micro computerized tomography (CT) scan-generated three-dimensional (3-D) image of fibers. However, the large size of the CT scan-generated 3-D image often makes it difficult to separate each fiber and extract end point information. In this article, a novel method to address this challenge is presented. The micro-CT images were broken into finite volume, reducing data size, and then each fiber was reduced to its own centerline, using Mimics ® Innovation Suite (Materialise NV), further reducing the data size. These 3-D centerlines were then used to quantify the second-order orientation tensor. The results from the proposed method are compared with the measurements using well-established industry standard approach called the method of ellipses for validation. The key challenges in estimating the fiber orientation are identified and future improvements are proposed.
Fiber faceplates to mitigate diffraction effects in an imaging snapshot polarimeter (2008)

We investigate the advantages of employing a fiber faceplate in a snapshot polarimetry system. Our previous work at
Sandia National Laboratories indicates that diffraction and propagation between the micropolarizer array, the microwaveplate
array, and the Focal Plane Array (FPA) degrade performance, as quantified by the extinction ratio 1,2 .
Crosstalk between adjacent pixels due to diffraction increases uncertainty of the measured polarization states in a scene
of interest. These issues are exacerbated in the long-wavelength regime and as FPA pixel dimensions decrease.
One solution, since it minimizes propagation distance, is to construct the micropolarizer and micro-waveplate arrays on a
single substrate surface and to place this combination on the FPA 3 . This solution is a significant fabrication challenge
and decreases yield due to its serial assembly nature.
An alternative solution that would improve yield is to fabricate the micropolarizer on top of a fiber faceplate, place the
faceplate on the FPA with the micropolarizer facing away, then place the waveplate array on top of the micropolarizer.
The optical field that passes through the plane of the microwaveplate array and the micropolarizer array is guided to the
FPA plane, without suffering diffraction effects associated with free-space propagation. We will quantify the utility of
these proposed configurations with predicted imaging polarimetric system extinction ratios.
Sequential Prefetch Cache Sizing for Maximal Hit Rate (2010)

We propose a prefetch cache sizing module for use with any sequential prefetching scheme and evaluate its impact on the hit rate. Disk array caches perform sequential prefetching by loading data contiguous to I/O request data into the array cache. If the I/O workload has sequential locality, then data prefetched in response to sequential accesses in the workload will receive hits. Different schemes prefetch different data, so the prefetch cache size requirement varies. Moreover, the proportion of sequential and random requests in the workload and their interleaving pattern affects the size requirement. If the cache is too small, then prefetched data would get evicted from the cache before a request for the data arrives, thus lowering the hit rate. If the cache is too large, then valuable cache space is wasted. We present a simple sizing module that can be added to any prefetching scheme to ensure that the prefetch cache size is adequately matched to the requirement of the prefetching scheme on a dynamic workload comprising multiple streams. We analytically compute the maximal hit rate achievable by popular prefetching schemes and through simulations, show that our sizing module maintains the prefetch cache at a size that nearly achieves this maximal hit rate.
WIKIBrainStem: An online atlas to manually segment the human brainstem at the mesoscopic scale from ultrahigh field MRI (2021)

The brainstem is one of the most densely packed areas of the central nervous system in terms of gray, but also white, matter structures and, therefore, is a highly functional hub. It has mainly been studied by the means of histological techniques, which requires several hundreds of slices with a loss of the 3D coherence of the whole specimen. Access to the inner structure of the brainstem is possible using Magnetic Resonance Imaging (MRI), but this method has a limited spatial resolution and contrast in vivo. Here, we scanned an ex vivo specimen using an ultra-high field (11.7T) preclinical MRI scanner providing data at a mesoscopic scale for anatomical T2-weighted (100 µm and 185 µm isotropic) and diffusion-weighted imaging (300 µm isotropic). We then proposed a hierarchical segmentation of the inner gray matter of the brainstem and defined a set of rules for each segmented anatomical class. These rules were gathered in a freely accessible web-based application, WIKIBrainStem (https://fibratlas.univ-tours.fr/brainstems/index.html), for 99 structures, from which 13 were subdivided into 29 substructures. This segmentation is, to date, the most detailed one developed from ex vivo MRI of the brainstem. This should be regarded as a tool that will be complemented by future results of alternative methods, such as Optical Coherence Tomography, Polarized Light Imaging or histology… This is a mandatory step prior to segmenting multiple specimens, which will be used to create a probabilistic automated segmentation method of ex vivo, but also in vivo, brainstem and may be used for targeting anatomical structures of interest in managing some degenerative or psychiatric disorders.