gebhart/patrepeval huggingface dataset:
Development of a highly sensitive multicancer, targeted, cell-free DNA epigenomic assay for integrated screening of lung and colorectal cancer. (2022)

3542 Background: Cancer screening in asymptomatic individuals who meet guideline criteria has yielded reductions in cancer death rates. However, adherence to screening guidelines remains below targets set forth by leading health-care organizations. A blood-based multi-cancer screening assay with clinically meaningful sensitivity and specificity, in cancer types where early detection and intervention can save lives, that is integrated with existing clinical pathways may increase access to and adherence with guideline recommendations, ensuring more individuals benefit from these proven interventions. We evaluated the performance of a blood-based multi-cancer screening assay that interrogates cell-free DNA (cfDNA) methylation signatures for cancer detection and tissue of origin prediction in a set of tumor types where cancer screening can save lives. Methods: Whole blood from 1,607 individuals with and 3,298 individuals without cancer was obtained from multiple unique cohorts. Plasma-derived cfDNA was profiled using a custom assay that enriches fragments with dense CpG methylation and further depletes uninformative background molecules containing unmethylated CpGs. We utilized a broad genomic panel (16 Mb) targeting regions with low rates of methylation in individuals without cancer. The panel captures tumor-associated molecules and allows for high sensitivity of detection at low sequencing costs. A cross-validated analysis was used to estimate the performance of the predictive model upon the sample set. Classification thresholds corresponding to 90%, 95%, and 98% specificities were established using samples from individuals without a cancer diagnosis. Results: At 90% specificity, overall sensitivity for lung cancer detection was 92.1% (95% CI: 80-100%; 90.2% in Stage I/II disease (N = 82) and 93.1% in Stage III/IV disease (N = 159)) and 93.1% (CI: 88-98%) for CRC detection (92% in Stage I/II disease (N = 743) and 94.5% in Stage III/IV disease (N = 623)). Tissue of origin prediction evaluated at 98% specificity yielded accurate identification in 99% of CRC and 98% of lung cancers. Lung cancer histology was known for approximately 74% of the cohort. Across Stage I – IV cancers, at 90% specificity, sensitivity was 97.3% in lung squamous cancer (N = 73) and 86.8% in lung adenocarcinoma (N = 106). At 95% and 98% specificity thresholds, overall sensitivity was 86.3% (CI: 75-98%) and 66.4% (CI: 56-77%) for lung cancer and 85.7% (CI:81-91%) and 71.6% (CI: 67-76%) for CRC, respectively. Conclusions: This blood-based multi-cancer screening assay yields clinically meaningful sensitivity and specificity for early-stage cancers. This assay is undergoing further development to expand detection capabilities to additional cancer types where screening can save lives. Clinical evaluation in registrational screening trials is ongoing (SHIELD; NCT05117840).
Performance Evaluation of Multifunctional Energy Metering IC under Sinusoidal and Non-Sinusoidal Conditions (2006)

Low-cost handheld instruments performing a large variety of electrical measurements are recently appeared on the market. Their diffusion is mainly due to the availability of integrated circuits that carry out many measurement functions, thus simplifying the instrument implementation and reducing the costs. In this paper, the accuracy performances of an integrated circuit featuring rms and power measurements are evaluated under both sinusoidal and non-sinusoidal conditions. The implemented measurement bench and the obtained results are presented. The results show that the accuracy of the device under test is satisfactory for active power and current rms values, instead of the voltage channel accuracy is significantly worst.
High-throughput method for ear phenotyping and kernel weight estimation in maize using ear digital imaging (2018)

The method developed in this work provides an opportunity to significantly reduce the cost of selection in the breeding process, especially for resource constrained crop improvement programs and can be used to learn more about the genetic bases of grain yield determinants.
Examples of Homotopy Lie Algebras (2009)

We look at two examples of homotopy Lie algebras (also known as L_{\infty} algebras) in detail from two points of view. We will exhibit the algebraic point of view in which the generalized Jacobi expressions are verified by using degree arguments and combinatorics. A second approach using the nilpotency of Grassmann-odd differential operators Δto verify the homotopy Lie data is shown to produce the same results.
Targeted photodynamic therapy of established soft-tissue infections in mice (2004)

The worldwide rise in antibiotic resistance necessitates the development of novel antimicrobial strategies. Although many workers have used photodynamic therapy (PDT) to kill bacteria in vitro, the use of this approach has seldom been reported in vivo in animal models of infection. We have previously described the first use of PDT to treat excisional wound infections by Gram-negative bacteria in living mice. However these infected wound models used a short time after infection (30 min) before PDT. We now report on the use of PDT to treat an established soft-tissue infection in mice. We used Staphylococcus aureus stably transformed with a Photorhabdus luminescens lux operon (luxABCDE) that was genetically modified to be functional in Gram-positive bacteria. These engineered bacteria emitted bioluminescence allowing the progress of the infection to be monitored in both space and time with a lowlight imaging charged couple device (CCD) camera. One million cells were injected into one or both thigh muscles of mice that had previously been rendered neutropenic by cyclophosphamide administration. Twenty-four hours later the bacteria had multiplied more than one hundred-fold, and poly-L-lysine chlorin(e6) conjugate or free chlorin(e6) was injected into one area of infected muscle and imaged with the CCD camera. Thirty-minutes later red light from a diode laser was delivered as a surface spot or by interstitial fiber into the infection. There was a lightdose dependent loss of bioluminescence (to < 5% of that seen in control infections) not seen in untreated or light alone treated infections, but in some cases the infection recurred. Conjugate alone led to a lesser reduction in bioluminescence. Infections treated with free chlorin(e6) responded less and the infection subsequently increased over the succeeding days, probably due to PDT-mediated tissue damage. PDT-treated infected legs healed better than legs with untreated infections. This data shows that PDT may have applications in drug-resistant soft-tissue infections.
3D reconstruction of the optic nerve head using stereo fundus images for computer-aided diagnosis of glaucoma (2010)

The shape of the optic nerve head (ONH) is reconstructed automatically using stereo fundus color images by a robust stereo matching algorithm, which is needed for a quantitative estimate of the amount of nerve fiber loss for patients with glaucoma. Compared to natural scene stereo, fundus images are noisy because of the limits on illumination conditions and imperfections of the optics of the eye, posing challenges to conventional stereo matching approaches. In this paper, multi scale pixel feature vectors which are robust to noise are formulated using a combination of both pixel intensity and gradient features in scale space. Feature vectors associated with potential correspondences are compared with a disparity based matching score. The deep structures of the optic disc are reconstructed with a stack of disparity estimates in scale space. Optical coherence tomography (OCT) data was collected at the same time, and depth information from 3D segmentation was registered with the stereo fundus images to provide the ground truth for performance evaluation. In experiments, the proposed algorithm produces estimates for the shape of the ONH that are close to the OCT based shape, and it shows great potential to help computer-aided diagnosis of glaucoma and other related retinal diseases.
Quo vadis, „KECK“? – zum Problem von VERWENDUNGSBESCHRÄNKUNGEN im FREIEN WARENVERKEHR – (2010)

The Zeitschrift für Europarechtliche Studien (ZEuS) is published by the Europa-Institut, law department, of Saarland University since 1998. The concept of ZEuS is a wide one: the journal addresses current aspects and fundamental problems connected with European Integration, European law and International law. Consisting of articles especially in German and English which commentate on current developments in the law, ZEuS offers an ideal forum for contributors of both academic and professional backgrounds. Moreover, ZEuS makes a conscious effort to provide young academics and students with the opportunity to have their work published. Finally, all speeches held at the Europa-Institut are published in ZEuS.
Independent saturation of three TrpRS subsites generates a partially assembled state similar to those observed in molecular simulations (2020)

Two new crystal structures of Bacillus stearothermophilus tryptophanyl-tRNA synthetase (TrpRS) afford evidence that a closed interdomain hinge angle requires a covalent bond between AMP and an occupant of either pyrophosphate or tryptophan subsite. They also are within experimental error of a cluster of structures observed in a nonequilibrium molecular dynamics simulation showing partial active-site assembly. Further, the highest energy structure in a minimum action pathway computed by using elastic network models for Open and Pretransition state (PreTS) conformations for the fully liganded TrpRS monomer is intermediate between that simulated structure and a partially disassembled structure from a nonequilibrium molecular dynamics trajectory for the unliganded PreTS. These mutual consistencies provide unexpected validation of inferences drawn from molecular simulations.
QUANTITATIVE AND QUALITATIVE CHARACTERISATION OF THE ORGANIC AND NON-ORGANIC COMPONENTS OF HETEROTOPIC OSSIFICATION FROM BLAST-RELATED AMPUTEES (2015)

Heterotopic ossification (HO) is the formation of lamellar bone in extra-skeletal soft tissues. Its exact pathogenic mechanism remains elusive. Previous studies demonstrate observation only of HO at the microscopic scale. This study uses scanning electron microscopy (SEM), Back-scatter electron (BSE) imaging and mechanical testing to detail the organic and non-organic elements of HO, compared to normal bone, to guide stem cell and bio-modelling research into HO. Samples analysed were 5 military blast related HO patients, 5 control cadaveric samples (age and sex matched). Samples were imaged using SEM, BSE and the I13 beam Synchrotron x-ray diffraction scanner using validated quantitative and qualitative techniques of measurement. Appearances seen in HO compared to normal bone were characterised by the presence of a hyper-vascular network and high lacunae (osteocyte) counts, two distinct zones of bone mineral density distribution, with a tendency for hypermineralisation with kurtosis of the grey scale plots (mineral content as a weight percentage of Ca 2+ was calibrated to atomic weight of C, Al and HA). Direction of dependence and collagen orientation in HO suggest isotropic properties. This research demonstrates that HO is bone, however its characteristics suggest a high metabolic turnover and disorganised ultra-structure consistent with an inflammatory origin.
An Evaluation of CFD Cavitation Models using Streamline Data (2018)

In the present work, finite-rate cavitation models common to multi-phase computational fluid dynamics (CFD) are evaluated. These evaluations are based along streamlines extracted from benchmarked CFD. The results include comparative studies of: (1) full Rayleigh-Plesset equation (RPE), (2) simplifications to the RPE, and (3) other cavitation models. Additionally, using this approach, numerical uncertainty is evaluated at a much higher level than previously considered. In the context of developed cavitation, the present assessments elucidate similarities and differences between cavitation models and suggest mesh requirements are more demanding the normally considered.
T‐Lymphocyte‐derived interferon‐γ (IFN‐γ) mediates inflammatory responses to hypercholesterolemia, but is not the primary source of elevated plasma IFN‐γ (2007)

Hypercholesterolemia elicits an inflammatory phenotype in the microvasculature. T-lymphocytes mediate these responses via an IFN-γ dependent pathway. However it remains unclear whether plasma levels of IFN-γ are raised during hypercholesterolemia, and whether T-lymphocytes are the source of this circulating cytokine. We measured IFN-γ levels in wild-type (WT), immunodeficient (SCID) and IFN-γ deficient (IFN-γ ko) mice placed on a normal (ND) or high cholesterol diet (HC) for 2 wk and correlated these levels with microvascular inflammation. Separate SCID-HC mice received T-cells derived from WT or IFN-γ ko mice. HC led to a 5-fold increase in plasma IFN-γ levels in WT mice. This was not observed in SCID or IFN-γ ko mice. Transfer of WT T-cells to SCID mice restored IFN-γ levels to those observed in WT-HC, paralleling the microvascular inflammatory responses to HC. However SCID mice that received T-cells from IFN-γ ko mice also exhibited increased IFN-γ levels, in contrast to the abrogated microvascular inflammation in these mice. Our findings suggest that although T-lymphocyte-derived IFN-γ contributes to the microvascular responses to HC, these cells are unlikely to be the source of the accompanying rise in plasma IFN-γ. It remains unclear whether raised plasma levels of IFN-γ, perhaps from NK cells, are necessary for the IFN-γ-mediated microvascular inflammation elicited by HC. (Supported by R01 HL26441).
Yeasts of the Matador soils of Saskatchewan and their ability to use flavonoids (1971)

The numbers of yeasts of the soils of the Matador site of the International Biological Program, in southern Saskatchewan, varied from about 1400 to 10 000 cells/g soil in the surface layer and from 600 to 1800 cells/g in the subsurface layers. Most of the cultures isolated were Cryptococcus albidus and its variety diffluens, Cryptococcus laurentii, and Cryptococcus terreus. A few cultures of Cryptococcus dimennae, Rhodotorula minuta, Sporobolomyces pararoseus, and Sporobolomyces salmonicolor were also isolated. Most of the cultures isolated could use rutin and many of them used the other flavonoids tested. Many of them used phloroglucinol and a few used naphthalene.
Data from The PARP Inhibitor AZD2461 Provides Insights into the Role of PARP3 Inhibition for Both Synthetic Lethality and Tolerability with Chemotherapy in Preclinical Models (2023)

&lt;div&gt;Abstract&lt;p&gt;The PARP inhibitor AZD2461 was developed as a next-generation agent following olaparib, the first PARP inhibitor approved for cancer therapy. In &lt;i&gt;BRCA1&lt;/i&gt;-deficient mouse models, olaparib resistance predominantly involves overexpression of P-glycoprotein, so AZD2461 was developed as a poor substrate for drug transporters. Here we demonstrate the efficacy of this compound against olaparib-resistant tumors that overexpress P-glycoprotein. In addition, AZD2461 was better tolerated in combination with chemotherapy than olaparib in mice, which suggests that AZD2461 could have significant advantages over olaparib in the clinic. However, this superior toxicity profile did not extend to rats. Investigations of this difference revealed a differential PARP3 inhibitory activity for each compound and a higher level of PARP3 expression in bone marrow cells from mice as compared with rats and humans. Our findings have implications for the use of mouse models to assess bone marrow toxicity for DNA-damaging agents and inhibitors of the DNA damage response. Finally, structural modeling of the PARP3-active site with different PARP inhibitors also highlights the potential to develop compounds with different PARP family member specificity profiles for optimal antitumor activity and tolerability. &lt;i&gt;Cancer Res; 76(20); 6084–94. ©2016 AACR&lt;/i&gt;.&lt;/p&gt;&lt;/div&gt;
Electroreductive Radical Borylation of Unactivated (Hetero)Aryl Chlorides Without Light by Using Cumulene‐Based Redox Mediators** (2023)

Single-electron transfer (SET) plays a critical role in many chemical processes, from organic synthesis to environmental remediation. However, the selective reduction of inert substrates (E<sub>p/2</sub> <-2 V vs Fc/Fc<sup>+</sup> ), such as ubiquitous electron-neutral and electron-rich (hetero)aryl chlorides, remains a major challenge. Current approaches largely rely on catalyst photoexcitation to reach the necessary deeply reducing potentials or suffer from limited substrate scopes. Herein, we demonstrate that cumulenes-organic molecules with multiple consecutive double bonds-can function as catalytic redox mediators for the electroreductive radical borylation of (hetero)aryl chlorides at relatively mild cathodic potentials (approximately -1.9 V vs. Ag/AgCl) without the need for photoirradiation. Electrochemical, spectroscopic, and computational studies support that step-wise electron transfer from reduced cumulenes to electron-neutral chloroarenes is followed by thermodynamically favorable mesolytic cleavage of the aryl radical anion to generate the desired aryl radical intermediate. Our findings will guide the development of other sustainable, purely electroreductive radical transformations of inert molecules using organic redox mediators.
Corticotropin-Releasing Factor Binding to the Anterior Pituitary Receptor Is Modulated by Divalent Cations and Guanyl Nucleotides* (1986)

The binding of ovine CRF to bovine anterior pituitary membranes was characterized with the radioligand [Nle21, m-125I Tyr32]ovine CRF. The specific binding of CRF was increased by millimolar concentrations of the divalent cations Mg2+, Ca2+, and Mn2+, but was unaffected by the monovalent cations Na+, Ki+, and Li+. The increase in specific binding was not caused by a change in the affinity, but resulted from an apparent increased number of high affinity binding sites. In the presence of 10 mM Mg2+, CRF binding was saturable, specific, and of high affinity. At room temperature, under optimum conditions, binding reached equilibrium within 70 min, remained stable for at least 4 h, was reversible by excess unlabeled peptide, and was characterized by a Kd of 1.3 nM (0.74-2.4) and a total number of sites, R degree, of 90 fmol/mg protein (55-145). The affinity for the bovine membranes was the same as that for rat anterior pituitary membrane homogenates, and the concentrations of sites were similar. The relative binding affinities for the CRF receptor of selected agonists and antagonists in the bovine and rat systems were similar, and both showed good correlation with the relative in vitro potencies at stimulating or antagonizing, respectively, ACTH release from cultured rat anterior pituitary cells. The nonhydrolyzable GTP analog 5'-guanylylimidodiphosphate [Gpp(NH)p], caused a dose-dependent inhibition of bound radioligand, with an EC50 of about 0.5 microM. In the presence of 1 microM Gpp(NH)p, the number of high affinity CRF-binding sites was reduced, but the affinity was unchanged. In the presence of 5 microM Gpp(NH)p, there was no detectable high affinity binding, and the rate of dissociation of previously bound radioligand was increased. The other guanyl nucleotides, GTP and GDP, inhibited binding but to a lesser extent, whereas GMP and (Bu)2cGMP were ineffective. The inhibition was specific for guanyl nucleotides. In view of the established effects of guanyl nucleotides and divalent cations on adenylate cyclase-linked receptors, these data support the involvement of the adenylate cyclase system in the mechanism of action of CRF on the anterior pituitary.
Bidding Price-Based Transaction: Trust Establishment for Vehicular Fog Computing Service in Rural Area (2019)

In the time of passing through rural area, vehicles sometimes need to deal with blank spots of wireless network (4G/5G/WiFi/others). As a result, vehicles are unable to access fog computing service based on road side unit (RSU) infrastructure. To deal with this situation, vehicles utilize other vehicles' huge computational resource during their travel. However, it is not easy to put trust on other unknown vehicles since it can lead to a serious consequence for both user and server of vehicular fog computing service. In this paper, we attempt to fill gaps on establishing a trusted vehicular fog computing environment by mean of bidding price-based transaction (BPT) method. Through this method, vehicles do not need to encounter any trusted third party to have fog computing transaction with other vehicles. Moreover, every malicious activity may cause actors to lose bidding and trust, and then victim will gain redeem point as the compensation for receiving loss in transaction. In the end, this novel method is effective in limiting the number of potential attacks by mean of bidding price and payoff.
Multiple-input dc-dc converters to enhance local availability in grids using distributed generation resources (2007)

This paper analyzes a multiple-input converter topology with boost and buck-boost input legs that serves to integrate several different distributed generation sources into a common system dc bus. The multiple-input converter is arranged in modules that hold the common parts and in sub-modules that contain each input leg component. The result is a flexible and easily scalable system suitable for renewable energy sources. When compared with traditional highly reliable systems, such as telecom rectifiers and standard microgrid architectures, the proposed converter is inherently more reliable. Power budget equations are derived and studied. The theoretical analysis is verified with simulations and experimental results.
The fabrication of graphene-reinforced Al-based nanocomposites using high-pressure torsion (2018)

Metal matrix nanocomposites were fabricated by high-pressure torsion (HPT) using 5% graphene nanoplates as a reinforcement contained within an Al matrix. Powders were mixed and compacted at room temperature and then processed by HPT at three different temperatures of 298, 373 and 473 K. After processing, microstructural observations were undertaken to reveal the distributions of graphene in the matrix, the grain refinement in the aluminium and the nature of the graphene-aluminium interfaces. Tests were performed to measure the microhardness, the tensile stress-strain curves and the electrical conductivity. The results show that processing by HPT is advantageous because it avoids the sintering and high temperature deformation associated with other processing routes.
FPGA implementation of Token-based Self-timed processors: A case study (2017)

This paper describes an on-going work aiming at using FPGAs as a fast prototyping environment for Token-based Self-timed processors, inspired by the Octasic asynchronous design technique. Originally developed for Digital Signal Processing, this design technique is adapted here for an FPGA-based general purpose processor. The paper emphasizes improvements to existing FPGA implementation methodologies that address the incompatibilities between self-timed timing schemes and synchronous oriented place and route engines. It also presents a prototyping platform based on a Xilinx ZC706 board that enables functional verification, as well as runtime performance and power consumption measurements, of the reported Token-based Self-timed processor.