gebhart/patrepeval huggingface dataset:
Cell-free DNA profiling of metastatic prostate cancer reveals microsatellite instability, structural rearrangements and clonal hematopoiesis (2018)

Abstract Background There are multiple existing and emerging therapeutic avenues for metastatic prostate cancer, with a common denominator, which is the need for predictive biomarkers. Circulating tumor DNA (ctDNA) has the potential to cost-efficiently accelerate precision medicine trials to improve clinical efficacy and diminish costs and toxicity. However, comprehensive ctDNA profiling in metastatic prostate cancer to date has been limited. Methods A combination of targeted- and low-pass whole genome sequencing was performed on plasma cell-free DNA and matched white blood cell germline DNA in 364 blood samples from 217 metastatic prostate cancer patients. Results ctDNA was detected in 85.9% of baseline samples, correlated to line of therapy and was mirrored by circulating tumor cell enumeration of synchronous blood samples. Comprehensive profiling of the androgen receptor (AR) revealed a continuous increase in the fraction of patients with intra- AR structural variation, from 15.4% during first line mCRPC therapy to 45.2% in fourth line, indicating a continuous evolution of AR during the course of the disease. Patients displayed frequent alterations in DNA repair deficiency genes (18.0%). Additionally, the microsatellite instability phenotype was identified in 3.81% of eligible samples (≥0.1 ctDNA fraction). Sequencing of non-repetitive intronic- and exonic regions of PTEN, RB1 and TP53 detected biallelic inactivation in 47.5%, 20.3% and 44.1% of samples with ≥0.2 ctDNA fraction, respectively. Only one patient carried a clonal high-impact variant without a detectable second hit. Intronic high-impact structural variation was twice as common as exonic mutations in PTEN and RB1. Finally, 14.6% of patients presented false positive variants due to clonal hematopoiesis, commonly ignored in commercially available assays. Conclusions ctDNA profiles appear to mirror the genomic landscape of metastatic prostate cancer tissue and may cost-efficiently provide somatic information in clinical trials designed to identify predictive biomarkers. However, intronic sequencing of the interrogated tumor suppressors challenge the ubiquitous focus on coding regions and is vital, together with profiling of synchronous white blood cells, to minimize erroneous assignments which in turn may confound results and impede true associations in clinical trials.
Structural Determinants for Interaction with Three Different Effectors on the G Protein β Subunit (1997)

In the yeast two-hybrid system, a 100-residue fragment (beta1A) from the N terminus of the beta1 subunit interacts with domains specific to adenylyl cyclase 2 (AC2), the muscarinic atrial potassium channel (GIRK1), and phospholipase C-beta2 (PLC-beta2). Based on the crystal structure of the G protein, beta1A is composed of an N-terminal alpha helix, a loop, and five beta strands in which the C-terminal four beta strands form a beta sheet, the first of seven sheets that make up the propeller structure of the beta subunit. A mutant of beta1A (L4P, L7P, and L14P), in which the alpha helix was potentially destroyed, interacted poorly with the G protein gamma subunit but effectively with domains of AC2, GIRK1, and PLC-beta2. In contrast, another mutant of beta1A (S72A, D76A, and W82A), in which a network of hydrogen bonds was disrupted, interacted poorly with GIRK1 and PLC-beta2 domains, but effectively with the gamma subunit and the AC2 domain. These results suggest that the proper folding of the first five beta strands in the G protein beta subunit is a requirement for appropriately positioning residues that interact with GIRK1 and PLC-beta2. Furthermore, since mutations that potentially disrupted the folding of these beta strands did not affect interaction with AC2, the structural determinants on the G protein beta subunit for interaction with various effectors may be different.
Roles of PTEN (Phosphatase and Tensin Homolog) in Gastric Cancer Development and Progression (2014)

Gastric cancer is highly invasive, aggressively malignant, and amongst the most prevalent of all forms of cancer. Despite improved management strategies, early stage diagnosis of gastric cancer and accurate prognostic assessment is still lacking. Several recent reports have indicated that the pathogenesis of gastric cancer involves complex molecular mechanisms and multiple genetic and epigenetic alterations in oncogenes and tumor suppressor genes. Functional inactivation of the tumor suppressor protein PTEN (Phosphatase and Tensin Homolog) has been detected in multiple cases of gastric cancer, and already shown to be closely linked to the development, progression and prognosis of the disease. Inactivation of PTEN can be attributed to gene mutation, loss of heterozygosity, promoter hypermethylation, microRNA- mediated regulation of gene expression, and post-translational phosphorylation. PTEN is also involved in mechanisms regulating tumor resistance to chemotherapy. This review provides a comprehensive analysis of PTEN and its roles in gastric cancer, and emphasizes its potential benefits in early diagnosis and gene therapy-based treatment strategies.
Bone loss in response to long-term immobilisation (1978)

The histodynamic response to long-term "non-traumatic" immobilisation was studied in young adult Beagle dogs by means of radiomorphometry and histomorphometry, the right forelimb being encased in plaster and the left forelimb serving as a control. The dogs were killed at two, four, six, eight, twelve, sixteen, twenty, twenty-four, thirty-two and forty weeks and the third metacarpal, radius, ulna and humerus removed for analysis of the contributions of the periosteal, haversian and endosteal envelopes to the bone loss at the mid-diaphysis. The bone mass responded to long-term immobilisation in three stages. First there was a rapid initial loss of bone, reaching its maximum (some 16 per cent of original mass) at six weeks, to which all three bone envelopes, to some extent, contributed. A rapid reversal followed, the bone mass approaching the control values between eight and twelve weeks after immobilisation. A second stage of slower but longer lasting bone loss ended twenty-four to thirty-two weeks after immobilisation; the periosteal envelope was the main contributor (80 to 90 per cent of the total loss). The third stage was characterised by maintenance of the bone mass which had been reduced by some 30 to 50 per cent of original values. This pattern was qualitatively similar in all four bones but the distal bones lost more bone than the proximal bones. The extent of resorption surface and the total histologically "active" periosteal envelope increased parallel to the phases of bone loss. The linear mineralisation rate did not differ significantly between the experimental and control sides.
Mapping Real Time Applications on NoC Architecture with Hybrid Multi-objective Algorithm (2010)

International audience
Structural and Biochemical Evidence that Scrapie-associated Fibrils Assemble in vivo (1989)

Scrapie-associated fibrils (SAF) are a ubiquitous pathological feature of brains affected by scrapie and the other scrapie-like agents. They are composed of PrP, a heterogeneous glycoprotein which is also present in normal brain but not as SAF. The PrP protein associated with SAF is partially resistant to proteinase K, whereas the soluble form is not. It has been proposed that SAF do not exist as such in vivo, but rather self-assemble from subunit structures liberated from membranes by detergent extraction during purification. We have purified SAF by a method that does not employ proteinase K. We show that the PrP protein from infected but not uninfected brain is partially resistant to protease digestion before and after detergent extraction. Likewise, SAF can be sheared by sonication before or after detergent extraction. In addition, SAF from mice infected with different strains of scrapie have different sedimentation properties. Since SAF-dependent properties exist before detergent extraction, then so must SAF. They are therefore not a detergent-induced artefact but most probably assemble in vivo.
Chemical composition of nucleosomes among domains of calf thymus chromatin differing in micrococcal nuclease accessibility and solubility properties. (1981)

Calf thymus chromatin was fractionated by the Sanders' procedure ((1978) J. Cell Biol. 79, 97-109). this procedure involves sequential elutions of micrococcal nuclease-digested nuclei with buffers of increasing ionic strength. Through the use of the nuclei nick translation technique of Levitt et al. (Levitt, A., Axel, R., and Cedar, H. (1979) Dev. Biol. 69, 496-505) which specifically labels the transcriptionally competent regions of the chromosome, the lowest salt eluted, micrococcal nuclease-sensitive chromatin fraction, was found to be enriched in transcriptionally competent chromatin. This chromatin fraction contained approximately equimolar amounts of the core histones and low amounts of histone H1. In addition, this fraction was enriched both in the acetylated species of histone H4 and in the high mobility group (HMG) proteins 14 and 17, but it was depleted in 5-methylcytosine. As the ionic strength of the elution buffers increased, chromatin fractions from less micrococcal nuclease-sensitive chromatin domains were eluted. The nuclease-insensitive fractions were enriched in the unacetylated species of histone H4, 5-methylcytosine, and histone H1. Although these fractions had a smaller proportion of nucleosomes containing HMG-14 and HMG-17, they contained about 50% of the total HMG-14 and HMG-17 population.
A new spectral ratio method using narrow band coda envelopes: Evidence for non‐self‐similarity in the Hector Mine sequence (2007)

The use of local and regional S ‐wave coda is shown to provide stable amplitude ratios that better constrains source differences between event pairs. We first compared amplitude ratio performance between local and near‐regional S and coda waves in the San Francisco Bay region for moderate‐sized events, then applied the coda spectral ratio method to the 1999 Hector Mine mainshock and its larger aftershocks. We find (1) average amplitude ratio standard deviations using coda are ∼0.05 to 0.12, roughly a factor of 3 smaller than direct S ‐waves for 0.2 < f < 15.0 Hz; (2) coda spectral ratios for the M w 7.0 Hector Mine earthquake and its aftershocks show a clear departure from self‐similarity, consistent with other studies using the same datasets; and (3) event‐pairs (Green's function and target events) can be separated by ∼25 km for coda amplitudes without any appreciable degradation, in sharp contrast to direct waves.
Reduced mammary tumor progression in a transgenic mouse model fed an isoflavone‐poor soy protein concentrate (2008)

Dietary exposure to soy has been associated with reduced breast cancer incidence. Soy isoflavones and protein components, such as protease inhibitors and the lunasin peptide, have been indicated as potential agents reducing carcinogenesis. In this study, the effect of soy-based diets was evaluated in a transgenic mouse model of breast carcinoma, overexpressing the neu oncogene. Neu female mice were fed for 20 wk a soy- and isoflavone-free diet (IFD), 4RF21 laboratory mouse diet, soy-based, thus isoflavone-rich (STD), or AIN-76-based semisynthetic diets with a soy protein isolate (SPI) or an isoflavone-poor soy protein concentrate (IPSP) as protein source. Mice were then sacrificed and tumors removed. Mammary tumor weights were not different in SPI versus IFD and STD fed mice. In contrast, mice fed IPSP showed reduced tumor progression versus IFD and STD groups (p < 0.05). Moreover, IPSP fed mice showed lower bromo-2'-deoxyuridine (BrdU) incorporation into breast tumor cells compared to STD and SPI fed animals (p < 0.02). Lung metastases were detected in 80% of IFD fed mice, in 70% of mice fed STD and SPI, and only in 50% of the IPSP fed animals. These results indicate that a diet containing an isoflavone-poor soy protein concentrate may inhibit breast tumor progression and metastasis development.
Reconstruction of two-dimensional axisymmetric inhomogeneous media (1993)

The author has used transverse electric measurements on the symmetry axis of an axisymmetric inhomogeneous medium to reconstruct its two-dimensional complex permittivity distribution. The distorted Born iterative method is applied to solve the nonlinear inversion problem, and the numerical mode-matching method is used to solve the forward problem in each iteration. It is shown through numerical examples that good imaging results can be obtained by using very simple measurements on the axis of symmetry.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">></ETX>
Interactions in the Tomato Rhizosphere of Two<i>Pseudomonas</i>Biocontrol Strains with the Phytopathogenic Fungus<i>Fusarium oxysporum</i>f. sp.<i>radicis-lycopersici</i> (2003)

The fungus Fusarium oxysporum f. sp. radicis-lycopersici causes foot and root rot of tomato plants, which can be controlled by the bacteria Pseudomonas fluorescens WCS365 and P. chlororaphis PCL1391. Induced systemic resistance is thought to be involved in biocontrol by P. fluorescens WCS365. The antifungal metabolite phenazine-1-carboxamide (PCN), as well as efficient root colonization, are essential in the mechanism of biocontrol by P. chlororaphis PCL1391. To understand the effects of bacterial strains WCS365 and PCL1391 on the fungus in the tomato rhizosphere, microscopic analyses were performed using different autofluorescent proteins as markers. Tomato seedlings were inoculated with biocontrol bacteria and planted in an F. oxysporum f. sp. radicis-lycopersici-infested gnotobiotic sand system. Confocal laser scanning microscope analyses of the interactions in the tomato rhizosphere revealed that i) the microbes effectively compete for the same niche, and presumably also for root exudate nutrients; ii) the presence of either of the two bacteria negatively affects infection of the tomato root by the fungus; iii) both biocontrol bacteria colonize the hyphae extensively, which may represent a new mechanism in biocontrol by these pseudomonads; and iv) the production of PCN by P. chlororaphis PCL1391 negatively affects hyphal growth and branching, which presumably affects the colonization and infecting ability of the fungus.
Immune Modulation by Zoledronic Acid in Human Myeloma: An Advantageous Cross-Talk between Vγ9Vδ2 T Cells, αβ CD8+ T Cells, Regulatory T Cells, and Dendritic Cells (2011)

Vγ9Vδ2 T cells play a major role as effector cells of innate immune responses against microbes, stressed cells, and tumor cells. They constitute <5% of PBLs but can be expanded by zoledronic acid (ZA)-treated monocytes or dendritic cells (DC). Much less is known about their ability to act as cellular adjuvants bridging innate and adaptive immunity, especially in patients with cancer. We have addressed this issue in multiple myeloma (MM), a prototypic disease with several immune dysfunctions that also affect γδ T cells and DC. ZA-treated MM DC were highly effective in activating autologous γδ T cells, even in patients refractory to stimulation with ZA-treated monocytes. ZA inhibited the mevalonate pathway of MM DC and induced the intracellular accumulation and release into the supernatant of isopentenyl pyrophosphate, a selective γδ T cell activator, in sufficient amounts to induce the proliferation of γδ T cells. Immune responses against the tumor-associated Ag survivin (SRV) by MHC-restricted, SRV-specific CD8(+) αβ T cells were amplified by the concurrent activation of γδ T cells driven by autologous DC copulsed with ZA and SRV-derived peptides. Ancillary to the isopentenyl pyrophosphate-induced γδ T cell proliferation was the mevalonate-independent ZA ability to directly antagonize regulatory T cells and downregulate PD-L2 expression on the DC cell surface. In conclusion, ZA has multiple immune modulatory activities that allow MM DC to effectively handle the concurrent activation of γδ T cells and MHC-restricted CD8(+) αβ antitumor effector T cells.
Gordon Intake Gate (1982)

The intake gate for the Gordon Power Station is an unusual design which evolved as a solution to the vibration problems which have troubled many other cylinder type gate installations around the world. The gate is 8.23 meters in diameter and operates under a head of 60 meters. This paper describes the design and construction of the gate and outlines the features which were incorporated in order to achieve a reliable fast-closure device for protection of the power station.
Two kinds of lithotrophs missing in nature (1977)

Abstract Two groups of lithotrophic bacteria, the existence of which may be expected on evolutionary and thermodynamical grounds, have not yet been detected: (A) photosynthetic, anaerobic, ammonia bacteria, analogous to coloured sulphur bacteria, and (B) chemosynthetic bacteria that oxidize ammonia to nitrogen with O 2 or nitrate as oxidant.
LONG-TERM MORTALITY FOLLOW-UP OF ARMYRECRUITS WHO RECEIVED ADJUVANT INFLUENZA VIRUS VACCINE IN 1951–19531 (1972)

Beebe, G. W. (Follow-up Agency, National Research Council, Wash., D.C. 20418), A. H. Simon and S. Vivona. Long-term mortality follow-up of Army recruits who received adjuvant influenza virus vaccine in 1951–1953. Am J Epidemiol 95: 337–346, 1972.—Although studies sponsored by the Commission on Influenza, Armed Forces Epidemiological Board have shown that the effectiveness of influenza virus vaccine can be greatly increased by emulsification in light mineral oil, concern as to the safety of oil-adjuvant preparations has prevented their acceptance for routine use pending definitive long-term testing of both emulsifying agent (Arlacel A) and mineral oil (Drakeol) in experimental animals. In a previous 10-year follow-up study based on Salk's 1951–1953 randomized trials of the adjuvant influenza virus vaccine at Ft. Dix, there was no suggestion of a mortality effect attributable to the adjuvant. In the present study the mortality follow-up has been extended through April 1969, 16 to 18 years after vaccination. The vaccine groups have been compared with respect to all diagnoses listed on the death certificates, autopsy protocols, and terminal hospital records. The findings are essentially negative with respect to malignant neoplasms, allergic diseases, and collagen diseases. In addition, there is no evidence that men known to have had the cyst-like reaction at the site of the inoculation, or thought to have had allergic reactions mediated by the adjuvant vaccine, have experienced a higher mortality risk.
The MIME Multipart/Related Content-type (1995)

The Multipart/Related content-type provides a common mechanism for representing objects that are aggregates of related MIME body parts.This document defines the Multipart/Related content-type and provides examples of its use.
Blockchain for the Internet of Vehicles: A Decentralized IoT Solution for Vehicles Communication Using Ethereum (2020)

The concept of smart cities has become prominent in modern metropolises due to the emergence of embedded and connected smart devices, systems, and technologies. They have enabled the connection of every "thing" to the Internet. Therefore, in the upcoming era of the Internet of Things, the Internet of Vehicles (IoV) will play a crucial role in newly developed smart cities. The IoV has the potential to solve various traffic and road safety problems effectively in order to prevent fatal crashes. However, a particular challenge in the IoV, especially in Vehicle-to-Vehicle (V2V) and Vehicle-to-Infrastructure (V2I) communications, is to ensure fast, secure transmission and accurate recording of the data. In order to overcome these challenges, this work is adapting Blockchain technology for real time application (RTA) to solve Vehicle-to-Everything (V2X) communications problems. Therefore, the main novelty of this paper is to develop a Blockchain-based IoT system in order to establish secure communication and create an entirely decentralized cloud computing platform. Moreover, the authors qualitatively tested the performance and resilience of the proposed system against common security attacks. Computational tests showed that the proposed solution solved the main challenges of Vehicle-to-X (V2X) communications such as security, centralization, and lack of privacy. In addition, it guaranteed an easy data exchange between different actors of intelligent transportation systems.
The initiation of metabolic inflammation in childhood obesity (2017)

An understanding of the events that initiate metabolic inflammation (metainflammation) can support the identification of targets for preventing metabolic disease and its negative effects on health. There is ample evidence demonstrating that the initiating events in obesity-induced inflammation start early in childhood. This has significant implications on our understanding of how early life events in childhood influence adult disease. In this Review we frame the initiating events of metainflammation in the context of child development and discuss what this reveals about the mechanisms by which this unique form of chronic inflammation is initiated and sustained into adulthood.
Risk Factors for Group B Streptococcal Disease in Adults (1995)

Several chronic conditions were independently associated with group B streptococcal disease, and most case-patients had at least one of these conditions. If group B streptococcal vaccines being developed for prevention of neonatal disease are protective in adults, a vaccination strategy targeting those at highest risk has the potential to substantially reduce the burden of invasive group B streptococcal infection in adults.
Prognostic and health management for avionics (2005)

This paper describes methodologies and tools to anticipate in real-time, the onset of failures in electronic equipment. Currently developed techniques for prognostics and health management (PHM), depend on the observation of precursor variables and an imputation from them of impending failure. In electronic systems, such variables are difficult, impossible or expensive to obtain, so we propose a model-based technique utilizing embedded life models and environmental information obtained from aircraft mounted sensors that measure those parameters that most significantly accelerate failure in electronics, i.e. temperature, temperature variation, vibration and shock. This technology is referred to throughout this paper as electronics prognostics and health management (ePHM).
Low-Level Laser Therapy for Reducing the Hip, Waist, and Upper Abdomen Circumference of Individuals with Obesity (2016)

Based on these results, the device was cleared by the U.S. Food and Drug Administration as a noninvasive esthetic treatment for reduction of circumference of hips, waist, and upper abdomen when applied to individuals with a BMI between 30 and 40 kg/m<sup>2</sup>.
p‐type conduction in stacking‐fault‐free <i>m</i> ‐plane GaN (2007)

Abstract Transport measurements of p‐type m ‐plane GaN films grown on low extended‐defect density, free‐standing m ‐plane (10 $ \bar 1 $ 0) GaN substrates are presented. No significant anisotropy in in‐plane mobility was found for hole concentrations between 2.45 × 10 17 and 8.7 × 10 18 cm –3 . Since faulted, heteroepitaxial m ‐plane films showed significant anisotropy in electron and hole mobility a microstructural feature with anisotropic distribution (basal plane stacking faults) is discussed as a possible source of anisotropic scattering in non‐polar and semi‐polar films. (© 2007 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)