julilili42/papers huggingface dataset:
Limits on X-Ray Polarization at the Core of Centaurus A as Observed with the Imaging X-Ray Polarimetry Explorer
2022-08-01

Abstract We present measurements of the polarization of X-rays in the 2–8 keV band from the nucleus of the radio galaxy Centaurus A (Cen A), using a 100 ks observation from the Imaging X-ray Polarimetry Explorer (IXPE). Nearly simultaneous observations of Cen A were also taken with the Swift, NuSTAR, and INTEGRAL observatories. No statistically significant degree of polarization is detected with IXPE. These observations have a minimum detectable polarization at 99% confidence (MDP 99 ) of 6.5% using a weighted, spectral model-independent calculation in the 2–8 keV band. The polarization angle ψ is consequently unconstrained. Spectral fitting across three orders of magnitude in X-ray energy (0.3–400 keV) demonstrates that the SED of Cen A is well described by a simple power law with moderate intrinsic absorption ( N H ∼ 10 23 cm −2 ) and a Fe K α emission line, although a second unabsorbed power law is required to account for the observed spectrum at energies below 2 keV. This spectrum suggests that the reprocessing material responsible for this emission line is optically thin and distant from the central black hole. Our upper limits on the X-ray polarization are consistent with the predictions of Compton scattering, although the specific seed photon population responsible for the production of the X-rays cannot be identified. The low polarization degree, variability in the core emission, and the relative lack of variability in the Fe K α emission line support a picture where electrons are accelerated in a region of highly disordered magnetic fields surrounding the innermost jet.
Okadaic acid influences xenobiotic metabolism in HepaRG cells
2022-08-01

Okadaic acid (OA) is an algae-produced lipophilic marine biotoxin that accumulates in the fatty tissue of filter-feeding shellfish. Ingestion of contaminated shellfish leads to the diarrheic shellfish poisoning syndrome. Furthermore, several other effects of OA like genotoxicity, liver toxicity and tumor-promoting properties have been observed, probably linked to the phosphatase-inhibiting properties of the toxin. It has been shown that at high doses OA can disrupt the physical barrier of the intestinal epithelium. As the intestine and the liver do not only constitute a physical, but also a metabolic barrier against xenobiotic exposure, we here investigated the impact of OA on the expression of cytochrome P450 (CYP) enzymes and transporter proteins in human HepaRG cells liver cells in vitro at non-cytotoxic concentrations. The interplay of OA with known CYP inducers was also studied. Data show that the expression of various xenobiotic-metabolizing CYPs was downregulated after exposure to OA. Moreover, OA was able to counteract the activation of CYPs by their inducers. A number of transporters were also mainly downregulated. Overall, we demonstrate that OA has a significant effect on xenobiotic metabolism barrier in liver cells, highlighting the possibility for interactions of OA exposure with the metabolism of drugs and xenobiotics.
Denitrification‐Driven Transcription and Enzyme Production at the River‐Groundwater Interface: Insights From Reactive‐Transport Modeling
2022-08-01

Abstract Molecular‐biological data and omics tools have increasingly been used to characterize microorganisms responsible for the turnover of reactive compounds in the environment, such as reactive‐nitrogen species in groundwater. While transcripts of functional genes and enzymes are used as measures of microbial activity, it is not yet clear how they are quantitatively related to actual turnover rates under variable environmental conditions. As an example application, we consider the interface between rivers and groundwater which has been identified as a key driver for the turnover of reactive‐nitrogen compounds, that cause eutrophication of rivers and endanger drinking water production from groundwater. In the absence of measured data, we developed a reactive‐transport model for denitrification that simultaneously predicts the distributions of functional‐gene transcripts, enzymes, and reaction rates. Applying the model, we evaluate the response of transcripts and enzymes at the river‐groundwater interface to stable and dynamic hydrogeochemical regimes. While functional‐gene transcripts respond to short‐term (diurnal) fluctuations of substrate availability and oxygen concentrations, enzyme concentrations are stable over such time scales. The presence of functional‐gene transcripts and enzymes globally coincides with the zones of active denitrification. However, transcript and enzyme concentrations do not directly translate into denitrification rates in a quantitative way because of nonlinear effects and hysteresis caused by variable substrate availability and oxygen inhibition. Based on our simulations, we suggest that molecular‐biological data should be combined with aqueous geochemical data, which can typically be obtained at higher spatial and temporal resolution, to parameterize and calibrate reactive‐transport models.
Repeat expansions nested within tandem CNVs: a unique structural change in GLS exemplifies the diagnostic challenges of non-coding pathogenic variation
2022-08-01

Abstract Glutaminase deficiency has recently been associated with ataxia and developmental delay due to repeat expansions in the 5′UTR of the glutaminase (GLS) gene. Patients with the described GLS repeat expansion may indeed remain undiagnosed due to the rarity of this variant, the challenge of its detection and the recency of its discovery. In this study, we combined advanced bioinformatics screening of ~3000 genomes and ~1500 exomes with optical genome mapping and long-read sequencing for confirmation studies. We identified two GLS families, previously intensely and unsuccessfully analyzed. One family carries an unusual and complex structural change involving a homozygous repeat expansion nested within a quadruplication event in the 5′UTR of GLS. Glutaminase deficiency and its metabolic consequences were validated by in-depth biochemical analysis. The identified GLS patients showed progressive early-onset ataxia, cognitive deficits, pyramidal tract damage and optic atrophy, thus demonstrating susceptibility of several specific neuron populations to glutaminase deficiency. This large-scale screening study demonstrates the ability of bioinformatics analysis—validated by latest state-of-the-art technologies (optical genome mapping and long-read sequencing)—to effectively flag complex repeat expansions using short-read datasets and thus facilitate diagnosis of ultra-rare disorders.
Mirror exposure in binge-eating disorder: Changes in eating pathology and attentional biases.
2022-08-01

Evidence was found that stand-alone mirror exposure may contribute to improving shape concerns and the reduction of eating pathology in women with BED. Furthermore, mirror exposure impacts selective body-related attention even though generalizability of results is limited by small sample size, lack of statistical power, and expectancy effects due to comparison with WL. (PsycInfo Database Record (c) 2022 APA, all rights reserved).
Analysis of Somatosensory Profiles Using Quantitative Sensory Testing During Tonic and BurstDR Stimulation for the Treatment of Chronic Pain.
2022-08-01

In this study, it could be shown that, in some QST parameters and tested fiber functions, normalization tendencies were recognizable by using BurstDR or tonic SCS. However, BurstDR SCS seemed to be superior to tonic stimulation in this regard.
Optogenetic manipulation of cyclic guanosine monophosphate to probe phosphodiesterase activities in megakaryocytes
2022-08-01

Cyclic guanosine monophosphate (cGMP) signalling plays a fundamental role in many cell types, including platelets. cGMP has been implicated in platelet formation, but mechanistic detail about its spatio-temporal regulation in megakaryocytes (MKs) is lacking. Optogenetics is a technique which allows spatio-temporal manipulation of molecular events in living cells or organisms. We took advantage of this method and expressed a photo-activated guanylyl cyclase, Blastocladiella emersonii Cyclase opsin ( Be Cyclop), after viral-mediated gene transfer in bone marrow (BM)-derived MKs to precisely light-modulate cGMP levels. Be Cyclop-MKs showed a significantly increased cGMP concentration after illumination, which was strongly dependent on phosphodiesterase (PDE) 5 activity. This finding was corroborated by real-time imaging of cGMP signals which revealed that pharmacological PDE5 inhibition also potentiated nitric oxide-triggered cGMP generation in BM MKs. In summary, we established for the first-time optogenetics in primary MKs and show that PDE5 is the predominant PDE regulating cGMP levels in MKs. These findings also demonstrate that optogenetics allows for the precise manipulation of MK biology.
Hardware Accelerator and Neural Network Co-Optimization for Ultra-Low-Power Audio Processing Devices
2022-08-01

The increasing spread of artificial neural networks does not stop at ultralow-power edge devices. However, these very often have high computational demand and require specialized hardware accelerators to ensure the design meets power and performance constraints. The manual optimization of neural networks along with the corresponding hardware accelerators can be very challenging. This paper presents HANNAH (Hardware Accelerator and Neural Network seArcH), a framework for automated and combined hardware/software co-design of deep neural networks and hardware accelerators for resource and power-constrained edge devices. The optimization approach uses an evolution-based search algorithm, a neural network template technique and analytical KPI models for the configurable UltraTrail hardware accelerator template in order to find an optimized neural network and accelerator configuration. We demonstrate that HANNAH can find suitable neural networks with minimized power consumption and high accuracy for different audio classification tasks such as single-class wake word detection, multi-class keyword detection and voice activity detection, which are superior to the related work.
Postoperative complications and oncologic outcomes after multimodal therapy of localized high risk soft tissue sarcoma
2022-08-01

Abstract Background Standard therapy for localized high-risk soft tissue sarcoma includes surgical resection and neoadjuvant or adjuvant radiation therapy (+/-chemotherapy and locoregional hyperthermia). No difference in oncologic outcomes for patients treated with neoadjuvant and adjuvant radiation therapy was reported, whereas side effect profiles differ. The aim of this analysis was to analyse oncologic outcomes and wound healing complications in patients treated with multimodal treatment. Methods Oncologic outcomes and major wound complications (MWC, subclassified as wound healing disorder, infection, abscess, fistula, seroma and hematoma) were evaluated in all 84 patients with localized high-risk soft tissue sarcoma undergoing multimodal treatment, and also separately for the subgroup of lower extremity tumors. Clinical factors and treatment modalities (especially neoadjuvant versus adjuvant radiotherapy) were evaluated regarding their prognostic value and impact on postoperative wound complications. Results Oncologic outcome was dependent on tumor localization (worse for retroperitoneal sarcomas) and number of high risk features (tumor size, depth to superficial fascia and grading), but not on therapy sequencing (however with higher risk patients in the neoadjuvant group). Different risk factors influenced different subclasses of wound healing complications. No difference in MWC-rate in the whole cohort was found between patients treated with neoadjuvant and adjuvant radiation therapy (31.4% vs. 18.2%, p = 0.168). Except for wound infections, no significant differences were observed between neoadjuvant and adjuvant therapy. Diabetes was confirmed as a major risk factor for immune-related wound complications. Conclusion Rates of major wound complications in this cohort are comparable to published data, higher rates of wound infections were observed after neoadjuvant radiotherapy. Patient age and diabetes seem to be major risk factors. The number of risk factors for high risk soft tissue sarcoma seem to influence oncologic outcomes. Neoadjuvant treatment increases the risk only for wound infection treated with oral or intravenous antibiotic therapy and appears to be a safe option at an experienced tertiary center in absence of other risk factors.
A narrative review of the role of glucocorticoid receptors in prostate cancer: developments in last 5 years
2022-08-01

Various GR isoforms may play an important part in the development of CRPC, whose mechanism remains unclear. Most clinical trials have focused on the use of prednisone in the last 5 years. The efficacy of prednisone and dexamethasone is similar.
A Baseline Cellular Antiviral State Is Maintained by cGAS and Its Most Frequent Naturally Occurring Variant rs610913
2022-08-01

Abstract Upon recognition of aberrantly located DNA, the innate immune sensor cyclic GMP-AMP synthase (cGAS) activates stimulator of IFN genes (STING)/IFN regulatory factor (IRF)3–driven antiviral responses. In this study, we characterized the ability of a specific variant of the human cGAS-encoding gene MB21D1, rs610913, to alter cGAS-mediated DNA sensing and viral infection. rs610913 is a frequent G&amp;gt;T polymorphism resulting in a P261H exchange in the cGAS protein. Data from the International Collaboration for the Genomics of HIV suggested that rs610913 nominally associates with HIV-1 acquisition in vivo. Molecular modeling of cGAS(P261H) hinted toward the possibility for an additional binding site for a potential cellular cofactor in cGAS dimers. However, cGAS(wild-type [WT]) or cGAS(P261H)-reconstituted THP-1 cGAS knockout cells shared steady-state expression of IFN-stimulated genes, as opposed to cells expressing the enzymatically inactive cGAS(G212A/S213A). Accordingly, cGAS(WT) and cGAS(P261H) cells were less susceptible to lentiviral transduction and infection with HIV-1, HSV-1, and Chikungunya virus as compared with cGAS knockout or cGAS(G212A/S213A) cells. Upon DNA challenge, innate immune activation appeared to be mildly reduced upon expression of cGAS(P261H) compared with cGAS(WT). Finally, DNA challenge of PBMCs from donors homozygously expressing rs610913 provoked a trend toward a slightly reduced type I IFN response as compared with PBMCs from GG donors. Taken together, the steady-state activity of cGAS maintains a baseline antiviral state rendering cells more refractory to IFN-stimulated gene–sensitive viral infections. rs610913 failed to grossly differ phenotypically from the WT gene, suggesting that cGAS(P261H) and WT cGAS share a similar ability to sense viral infections in vivo.
The DKTK EXLIQUID consortium – exploiting liquid biopsies to advance cancer precision medicine for molecular tumor board patients
2022-08-01

Abstract Testing for genetic alterations in tumor tissue allows clinicians to identify patients who most likely will benefit from molecular targeted treatment. EXLIQUID – exploiting liquid biopsies to advance cancer precision medicine – investigates the potential of additional non-invasive tools for guiding therapy decisions and monitoring of advanced cancer patients. The term “liquid biopsy” (LB) refers to non-invasive analysis of tumor-derived circulating material such as cell-free DNA in blood samples from cancer patients. Although recent technological advances allow sensitive and specific detection of LB biomarkers, only few LB assays have entered clinical routine to date. EXLIQUID is a German Cancer Consortium (DKTK)-wide joint funding project that aims at establishing LBs as a minimally-invasive tool to analyze molecular changes in circulating tumor DNA (ctDNA). Here, we present the structure, clinical aim, and methodical approach of the new DKTK EXLIQUID consortium. Within EXLIQUID, we will set up a multicenter repository of high-quality LB samples from patients participating in DKTK MASTER and local molecular tumor boards, which use molecular profiles of tumor tissues to guide targeted therapies. We will develop LB assays for monitoring of therapy efficacy by the analysis of tumor mutant variants and tumor-specific DNA methylation patterns in ctDNA from these patients. By bringing together LB experts from all DKTK partner sites and exploiting the diversity of their particular expertise, complementary skills and technologies, the EXLIQUID consortium addresses the challenges of translating LBs into the clinic. The DKTK structure provides EXLIQUID a unique position for the identification of liquid biomarkers even in less common tumor types, thereby extending the group of patients benefitting from non-invasive LB testing. Besides its scientific aims, EXLIQUID is building a valuable precision oncology cohort and LB platform which will be available for future collaborative research studies within the DKTK and beyond.
Comparative embryogenesis in ungulate domesticated species
2022-08-01

Abstract We compared embryogenesis of five species of domesticated even‐toed and one odd‐toed ungulate and used a phylogenetic framework to contextualize such comparison. Organ systems that occur relatively earlier in embryogenesis generally have more time to develop and therefore are found to be more mature at birth when compared to structures that appear later in development. We hypothesized that the less mature the animals' organs are at birth, the more they are susceptible to artificial selection. The horse had the most mature organs at birth, followed by cattle, reindeer, sheep/goat, and pig. This pattern of maturity could be observed almost during the entire development. Heterochronic shifts among species were observed only after fur starts to develop. Changes in the fur coloration are one of the first observable signs of domestication and the heterochrony of this trait may be related to the effects on neural crest‐derived pigment cells by artificial selection. The six ungulate species also differ in the relative duration of their weaning period and the potential extent of its artificial shortening. We put all these traits in the context of their inherited evolutionary characteristics and artificial domestication process. Related to their altriciality, carnivoran domesticates, which also belong to Scrotifera, are less mature at birth than all domesticated ungulates. Although we detected clear character correlations to life history traits, it is impossible based on the present data, to trace specific exaptations to the domestication process. We hypothesize a deep time developmental penetration of adult characters into embryogenesis.
The Cultural and Chronostratigraphic Context of a New Leaf Point from Hohle Fels Cave in the Ach Valley of Southwestern Germany
2022-08-01

During the summer of 2020 the excavation team at Hohle Fels Cave in the Ach Valley of southwestern Germany recovered a leaf point (in German Blattspitze) made from gray Jurassic chert. The find is well-preserved and remarkable for a number of reasons. First this is the only leaf point recovered by a modern excavation in the Swabian Jura, and is the first leaf point discovered in situ since 1936, when Gustav Riek’s crew recovered two well-preserved leaf points at the excavation of Haldenstein Cave in the Lone Valley. The leaf point and associated finds originate from archaeological horizon (AH) X, 120 cm below the base of the rich Aurignacian deposits at the site that dates with radiocarbon to ca. 42 ka cal BP. Four ESR dates made on the teeth of large mammals from AH IX overlying the new leaf point yielded an average age of 62.5 ± 4 ka BP. This date represents a minimum age for the new horizons, which based on convention would be placed in the cultural taxonomic unit of the Blattspitzengruppe. Since the Blattspitzengruppe is typically interpreted as the last Middle Paleolithic cultural unit, we were intrigued to find an assemblage containing a Blattspitze in such an early chronostratigraphic context. While in Germany the Blattspitzengruppe is usually associated with the end of the Middle Paleolithic, many researchers across Europe have described these leaf point assemblages as being transitional industries at the interface between the Middle and Upper Paleolithic. Historically, some authors have even suggested a degree of cultural continuity between leaf point assemblages of the Middle and Upper Paleolithic. Here we present the stratigraphic and chronological context of the AH X and provide a preliminary description of the material cultural record from this horizon. Keeping in mind that we so far have only excavated parts of 6 m2 of the new find horizon and the underlying find horizon AH XI, the paper provides initial observations that will need revision as the excavation proceeds. These findings suggest that leaf points represent a feature in the technological repertoire of the Late Pleistocene Neanderthals of southwestern Germany rather than a reliable cultural stratigraphic marker for the last phase of the Middle Paleolithic.
Dental Wear Evidence for Browsing and Grazing Dietary Traits in the Giant Deer from the Late Pleistocene of Central Europe
2022-08-01

The paleoecology of the giant deer (Megaloceros giganteus), including its dietary preferences, is poorly known, mainly because reconstructions based on morphological characteristics have produced contradictory results. In this study, we propose to reconstruct the diet of the giant deer from five archaeological sites located in Southern Germany and the Harz Mountains using microwear and mesowear analyses. We also include the results of a review of tooth wear data published during the past decade for ten localities in Europe. The objective is to provide a largescale vision of the diet of the giant deer and to analyse the spatial and temporal diversity of its dietary habits. According to our results, the dietary traits of the giant deer were found to range from leaf browsing to grass-dominated mixed feeding, depending on the vegetation available regionally and seasonally. The combination of the two proxies, mesowear and microwear, allowed us to characterize the dietary flexibility of the giant deer. Finally, we discuss the causes of its extirpation and conclude that its extinction was not likely driven by a narrow dietary niche.
Bose–Einstein condensation on hyperbolic spaces
2022-08-01

A well-known conjecture in mathematical physics asserts that the interacting Bose gas exhibits Bose–Einstein condensation (BEC) in the thermodynamic limit. We consider the Bose gas on certain hyperbolic spaces. In this setting, one obtains a short proof of BEC in the infinite-volume limit from the existence of a volume-independent spectral gap of the Laplacian.
WITHDRAWN: Interactions of organic phosphorus with soil minerals and the associated environmental impacts: A review
2022-08-01

The Publisher regrets that this article is an accidental duplication of an article that has already been published, https://doi.org/10.1016/j.pedsph.2022.08.001. The duplicate article has therefore been withdrawn. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our-business/policies/article-withdrawal