bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quantitative characterization of recombinase-based digitizer circuits enables predictable amplification of biological signals
Authors: Kiwimagi Katherine A. , Letendre Justin H. , Weinberg Benjamin H. , Wang Junmin , Chen Mingzhe , Watanabe Leandro , Myers Chris J. , Beal Jacob , Wong Wilson W. , Weiss Ron 
Published: July 2021

AbstractMany synthetic gene circuits are restricted to single-use applications or require iterative refinement for incorporation into complex systems. One example is the recombinase-based digitizer circuit, which has been used to improve weak or leaky biological signals. Here we present a workflow to quantitatively define digitizer performance and predict responses to different input signals. Using a combination of signal-to-noise ratio (SNR), area under a receiver operating characteristic curve (AUC), and fold change (FC), we evaluate three small-molecule inducible digitizer designs demonstrating FC up to 508x and SNR up to 3.77 dB. To study their behavior further and improve modularity, we develop a mixed phenotypic/mechanistic model capable of predicting digitizer configurations that amplify a synNotch cell-to-cell communication signal (Δ SNR up to 2.8 dB). We hope the metrics and modeling approaches here will facilitate incorporation of these digitizers into other systems while providing an improved workflow for gene circuit characterization.
Three-dimensional CRISPR screening reveals epigenetic interaction with anti-angiogenic therapy
Authors: He Michael Y. , Halford Michael M. , Liu Ruofei , Roy James P. , Grant Zoe L. , Coultas Leigh , Thio Niko , Gilan Omer , Chan Yih-Chih , Dawson Mark A. , Achen Marc G. , Stacker Steven A. 
Published: July 2021

AbstractAngiogenesis underlies development, physiology and pathogenesis of cancer, eye and cardiovascular diseases. Inhibiting aberrant angiogenesis using anti-angiogenic therapy (AAT) has been successful in the clinical treatment of cancer and eye diseases. However, resistance to AAT inevitably occurs and its molecular basis remains poorly understood. Here, we uncover molecular modifiers of the blood endothelial cell (EC) response to a widely used AAT bevacizumab by performing a pooled genetic screen using three-dimensional microcarrier-based cell culture and CRISPR–Cas9. Functional inhibition of the epigenetic reader BET family of proteins BRD2/3/4 shows unexpected mitigating effects on EC survival and/or proliferation upon VEGFA blockade. Moreover, transcriptomic and pathway analyses reveal an interaction between epigenetic regulation and anti-angiogenesis, which may affect chromosomal structure and activity in ECs via the cell cycle regulator CDC25B phosphatase. Collectively, our findings provide insight into epigenetic regulation of the EC response to VEGFA blockade and may facilitate development of quality biomarkers and strategies for overcoming resistance to AAT.
Non-flipping DNA glycosylase AlkD scans DNA without formation of a stable interrogation complex
Authors: Ahmadi Arash , Till Katharina , Backe Paul Hoff , Blicher Pernille , Diekmann Robin , Schüttpelz Mark , Glette Kyrre , Tørresen Jim , Bjørås Magnar , Rowe Alexander D. , Dalhus Bjørn 
Published: July 2021

AbstractThe multi-step base excision repair (BER) pathway is initiated by a set of enzymes, known as DNA glycosylases, able to scan DNA and detect modified bases among a vast number of normal bases. While DNA glycosylases in the BER pathway generally bend the DNA and flip damaged bases into lesion specific pockets, the HEAT-like repeat DNA glycosylase AlkD detects and excises bases without sequestering the base from the DNA helix. We show by single-molecule tracking experiments that AlkD scans DNA without forming a stable interrogation complex. This contrasts with previously studied repair enzymes that need to flip bases into lesion-recognition pockets and form stable interrogation complexes. Moreover, we show by design of a loss-of-function mutant that the bimodality in scanning observed for the structural homologue AlkF is due to a key structural differentiator between AlkD and AlkF; a positively charged β-hairpin able to protrude into the major groove of DNA.
Age-dependent appearance of SARS-CoV-2 entry sites in mouse chemosensory systems reflects COVID-19 anosmia-ageusia symptoms
Authors: Brechbühl Julien , Lopes Ana Catarina , Wood Dean , Bouteiller Sofiane , de Vallière Aurélie , Verdumo Chantal , Broillet Marie-Christine 
Published: July 2021

AbstractCOVID-19 pandemic has given rise to a collective scientific effort to study its viral causing agent SARS-CoV-2. Research is focusing in particular on its infection mechanisms and on the associated-disease symptoms. Interestingly, this environmental pathogen directly affects the human chemosensory systems leading to anosmia and ageusia. Evidence for the presence of the cellular entry sites of the virus, the ACE2/TMPRSS2 proteins, has been reported in non-chemosensory cells in the rodent’s nose and mouth, missing a direct correlation between the symptoms reported in patients and the observed direct viral infection in human sensory cells. Here, mapping the gene and protein expression of ACE2/TMPRSS2 in the mouse olfactory and gustatory cells, we precisely identify the virus target cells to be of basal and sensory origin and reveal the age-dependent appearance of viral entry-sites. Our results propose an alternative interpretation of the human viral-induced sensory symptoms and give investigative perspectives on animal models.
Neutralising SARS-CoV-2 RBD-specific antibodies persist for at least six months independently of symptoms in adults
Authors: Wagner Angelika , Guzek Angela , Ruff Johanna , Jasinska Joanna , Scheikl Ute , Zwazl Ines , Kundi Michael , Stockinger Hannes , Farcet Maria R. , Kreil Thomas R. , Hoeltl Eva , Wiedermann Ursula 
Published: July 2021

Abstract
Background
In spring 2020, at the beginning of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic in Europe, we set up an assay system for large-scale testing of virus-specific and neutralising antibodies including their longevity.

Methods
We analysed the sera of 1655 adult employees for SARS-CoV-2-specific antibodies using the S1 subunit of the spike protein of SARS-CoV-2. Sera containing S1-reactive antibodies were further evaluated for receptor-binding domain (RBD)- and nucleocapsid protein (NCP)-specific antibodies in relation to the neutralisation test (NT) results at three time points over six months.

Results
We detect immunoglobulin G (IgG) and/or IgA antibodies reactive to the S1 protein in 10.15% (n = 168) of the participants. In total, 0.97% (n = 16) are positive for S1-IgG, 0.91% (n = 15) were S1-IgG- borderline and 8.28% (n = 137) exhibit only S1-IgA antibodies. Of the 168 S1-reactive sera, 8.33% (n = 14) have detectable RBD-specific antibodies and 6.55% (n = 11) NCP-specific antibodies. The latter correlates with NTs (kappa coefficient = 0.8660) but start to decline after 3 months. RBD-specific antibodies correlate most closely with the NT (kappa = 0.9448) and only these antibodies are stable for up to six months. All participants with virus-neutralising antibodies report symptoms, of which anosmia and/or dysgeusia correlate most closely with the detection of virus-neutralising antibodies.

Conclusions
RBD-specific antibodies are most reliably detected post-infection, independent of the number/severity of symptoms, and correlate with neutralising antibodies at least for six months. They thus qualify best for large-scale seroepidemiological evaluation of both antibody reactivity and virus neutralisation.
Facile synthesis of MgAl layered double hydroxides by a co-precipitation method for efficient nitrate removal from water: kinetics and mechanisms
Authors: Jiang Zhuwu , Wu Jiangnan , Liu Xinru , Yu Hai , Jiao Chengyuan , Shen Jyunhong , Pei Yanyan 
Published: July 2021

A series of MgAl-LDH as highly efficient adsorbents for removing low concentrations of NO3− were synthesized. The mechanism of NO3− removal has been comprehensively discussed in terms of its characterization, adsorption kinetics and thermodynamics.
Vertical compositional variations of liquid hydrocarbons in Titan’s alkanofers
Authors: Cordier Daniel , Bonhommeau David A. , Vu Tuan H. , Choukroun Mathieu , García-Sánchez Fernando 
Published: July 2021

Context.According to clues left by theCassinimission, Titan, one of the two Solar System bodies with a hydrologic cycle, may harbor liquid hydrocarbon-based analogs of our terrestrial aquifers, referred to as “alkanofers”.Aims.On the Earth, petroleum and natural gas reservoirs show a vertical gradient in chemical composition, established over geological timescales. In this work, we aim to investigate the conditions under which Titan’s processes could lead to similar situations.Methods.We built numerical models including barodiffusion and thermodiffusion (Soret’s effect) in N2+CH4+C2H6liquid mixtures, which are relevant for Titan’s possible alkanofers. Our main assumption is the existence of reservoirs of liquids trapped in a porous matrix with low permeability.Results.Due to the small size of the molecule, nitrogen seems to be more sensitive to gravity than ethane, even if the latter has a slightly larger mass. This behavior, noticed for an isothermal crust, is reinforced by the presence of a geothermal gradient. Vertical composition gradients, formed over timescales of between a fraction of a mega-year to several tens of mega-years, are not influenced by molecular diffusion coefficients. We find that ethane does not accumulate at the bottom of the alkanofers under diffusion, leaving the question of why ethane is not observed on Titan’s surface unresolved. If the alkanofer liquid was in contact with water-ice, we checked that N2did not, in general, impede the clathration of C2H6, except in some layers. Interestingly, we found that noble gases could easily accumulate at the bottom of an alkanofer.
Effects of respiratory muscle training in soccer players: a systematic review with a meta-analysis
Authors: León-Morillas Felipe , León-Garzón Martha Cecilia , del Mar Martínez-García María , Reina-Abellán Javier , Palop-Montoro María Victoria , de Oliveira-Sousa Silvana Loana 
Published: July 2021

AbstractRespiratory muscle training can improve strength and reduce respiratory muscle fatigue during high-intensity exercise. Little is known about the existing evidence in soccer players. A systematic review with a meta-analysis was performed to analyse the existing evidence on the effects of respiratory muscle training in soccer players. Two independent researchers reviewed 17 databases until July 2019. Inclusion criteria were controlled clinical trials (randomised or not), soccer players (professional or recreational), females and/or males, and respiratory muscle training compared with simulated or regular training groups. The methodological quality and quality of evidence were evaluated with the Cochrane Collaboration Tool and GRADE score, respectively. Statistical analysis was performed using the integral meta-analysis 3.3.070. Nine studies met the eligibility criteria. The meta-analysis was performed for eight variables related to respiratory muscle function, lung function and sports performance. Respiratory muscle training provided a significant improvement compared with simulated or regular training in maximal inspiratory buccal pressure (6 studies, SDM = 0.89; 95 % CI = 0.42, 1.35) and maximum consumption of oxygen (3 studies, SDM = 0.92; 95 % CI = 0.24; 1.61). No significant improvements were observed for other variables. The quality of the evidence was rated as low or very low.
Role of Benzylic Deprotonation in Nickel-Catalyzed Benzylic Dehydrogenation
Authors: Newhouse Timothy R. , Zhang Pengpeng , Cantrell Rachel L. 
Published: July 2021

AbstractAlkylarenes are readily functionalized via the corresponding benzylic anions. Benzylic anions have been used for a range of catalytic reactions, including Ni-catalyzed dehydrogenation. Interestingly, the employment of Zn(TMP)2 for slow and incomplete deprotonation of the benzylic position was observed. This manuscript describes a preliminary investigation into the deprotonation of heteroarenes and its relationship to Ni-catalyzed benzylic dehydrogenation.
Comparing Ipsilateral and Contralateral Laminotomy with Bilateral Decompression in Cases with Far Lateral Disk Herniation and Lumbar Spinal Stenosis
Authors: Akar Ezgi , Öğrenci Ahmet , Koban Orkun , Yılmaz Mesut , Dalbayrak Sedat 
Published: July 2021

Abstract
Introduction The aim of this study was to compare clinical results of bilateral decompression and laminotomy and contralateral laminotomy following discectomy from the same side in patients who have far lateral disk herniation and lumbar spinal stenosis at the same level.
Materials and Methods Twenty-four patients with far lateral disk herniation have been divided into two groups: group 1 (n = 14), those who have been through bilateral canal decompression with far lateral discectomy and ipsilateral approach, and group 2 (n = 10), those who have been through far lateral discectomy and bilateral decompression with unilateral approach from contralateral side. Early postoperative, 1st month, and 12th month back and leg pain Visual Analogue Scale (VAS) scores of the patients have been retrospectively evaluated.
Results There is no significant difference between 1st month back and leg pain VAS scores of the groups. But 12th month back and leg pain VAS scores of group 1 are significantly higher than 1st month VAS scores. Also, 12th month back and leg pain VAS scores of group 1 are significantly higher than group 1. In the scanning carried out when the complaints of eight patients in group 1 continued, pars interarticularis fracture has been observed on the side where the surgery has been performed (57.1%). Six of these eight patients have been through stabilization surgery (42.8%).
Conclusion Long-term postoperative results are better in cases who have been performed bilateral decompression with unilateral approach from contralateral side with median incision following paramedian incision discectomy in patients with far lateral disk herniation and spinal stenosis.
Understanding Speed–Accuracy Processing Dynamics in Aphasia Using Response Time Modeling
Authors: Evans William S. , Quique Yina M. 
Published: July 2021

AbstractPeople with aphasia demonstrate language impairments evident in both performance accuracy and processing speed, but the direct relationship between accuracy and speed requires further consideration. This article describes two recent attempts to make quantitative progress in this domain using response time modeling: the diffusion model (Ratcliff, 1978) applied to two-choice tasks and a multinomial ex-Gaussian model applied to picture naming. The diffusion model may be used to characterize core linguistic processing efficiency and speed–accuracy tradeoffs independently, and research suggests that maladaptive speed–accuracy tradeoffs lead to performance impairments in at least some people with aphasia. The multinomial ex-Gaussian response time model of picture naming provides a simple and straightforward way to estimate the optimal response time cutoffs for individual people with aphasia (i.e., the cutoff where additional time is unlikely to lead to a correct response). While response time modeling applied to aphasia research is at an early stage of development, both the diffusion model and multinomial ex-Gaussian response time model of picture naming show promise and should be further developed in future work. This article also provides preliminary recommendations for clinicians regarding how to conceptualize, identify, and potentially address maladaptive speed–accuracy tradeoffs for people with aphasia.
Laboratory Approaches to Test the Function of Antiphospholipid Antibodies
Authors: Szabó Gábor , Antal-Szalmás Péter , Kerényi Adrienne , Pénzes Krisztina , Bécsi Bálint , Kappelmayer János 
Published: July 2021

AbstractAntiphospholipid syndrome (APS) is a systemic autoimmune disorder caused by the presence of aPLs (antiphospholipid antibodies, i.e., anti-β2-glycoprotein I and anti-cardiolipin). Everyday practice in terms of laboratory diagnostics of APS includes determination of aPLs and well-known functional assays assessing for lupus anticoagulant (LA), in turn using various tests. According to recent guidelines, the recommended method for LA identification or exclusion is based on the Russell Viper Venom test and a sensitive activated partial thromboplastin time assay. Despite the fact that LA can be quantified in laboratory practice in this way, LA is still used as a binary parameter that is just one of the risk factors of thrombosis in APS. As of today, there are no other functional assays to routinely assess the risk of thrombosis in APS. It is well-known that APS patients display a wide range of clinical outcomes although they may express very similar laboratory findings. One way to solve this dilemma, could be if antibodies could be further delineated using more advanced functional tests. Therefore, we review the diagnostic approaches to test the function of aPLs. We further discuss how thrombin generation assays, and rotational thromboelastometry tests can be influenced by LA, and how experimental methods, such as flow cytometric platelet activation, surface plasmon resonance, or nano differential scanning fluorimetry can bring us closer to the puzzling interaction of aPLs with platelets as well as with their soluble protein ligand. These novel approaches may eventually enable better characterization of aPL, and also provide a better linkage to APS pathophysiology.
Clinical Application and Progress of Fecal Microbiota Transplantation in Liver Diseases: A Review
Authors: Gu Xinpei , Lu Qin , Zhang Chengcheng , Tang Zhewei , Chu Liuxi 
Published: July 2021

AbstractThe human gut harbors a dense and highly diverse microbiota of approximately 1,000 bacterial species. The interaction between the host and gut bacteria strongly influences human health. Numerous evidence suggest that intestinal flora imbalance is closely associated with the development and treatment of liver diseases, including acute liver injury and chronic liver diseases (cirrhosis, autoimmune liver disease, and fatty liver). Therefore, regulating the gut microbiota is expected to be a new method for the adjuvant treatment of liver diseases. Fecal microbiota transplantation (FMT) is defined as the transplantation of gut microbiota from healthy donors to sick patients via the upper or lower gastrointestinal route to restore the normal intestinal balance. In this study, we briefly review the current research on the gut microbiota and its link to liver diseases and then summarize the evidence to elucidate the clinical application and development of FMT in liver disease treatment.
Institutional and cultural determinants of speed of government responses during COVID-19 pandemic
Authors: Chen Diqiang , Peng Diefeng , Rieger Marc Oliver , Wang Mei 
Published: July 2021

AbstractThis article examines institutional and cultural determinants of the speed of government responses during the COVID-19 pandemic. We define the speed as the marginal rate of stringency index change. Based on cross-country data, we find that collectivism is associated with higher speed of government response. We also find a moderating role of trust in government, i.e., the association of individualism-collectivism on speed is stronger in countries with higher levels of trust in government. We do not find significant predictive power of democracy, media freedom and power distance on the speed of government responses.
Development of a deuterium-ice extruder for inertial confinement fusion experiments on the Z Facility
Authors: Awe T. J. , Perea L. , Hanson J. C. , York A. J. , Johnson D. W. , Benney D. J. , Crabtree J. A. 
Published: July 2021

A deuterium-ice extruder has been developed for inertial confinement fusion experiments on the Sandia National Laboratories Z Facility. The screw-driven extruder is filled via desublimation, where a slow flow of deuterium gas enters the extruder cavity and freezes to the walls without entering the liquid phase. Ice generated in this manner is optically clear, demonstrating its high uniformity. When the extruder cavity is filled with ice, the screw is driven downward, closing off the gas-fill line. With the ice cavity isolated, further screw rotation compresses the deuterium through a nozzle, extruding a fiber. Fiber diameters ranging from 200 to 500 µm have been extruded to lengths of 1.5 feet before hitting the vacuum chamber floor. The fiber straightness improves with the nozzle length-to-diameter aspect ratio. Deuterium-ice fibers can persist in high vacuum for more than 10 min before breaking free from the nozzle. The peripheral infrastructure required for Z experimental operations is under development. An in-vacuum stepper-motor-based drive system will allow remote operation, and a translating cathode will ensure proper placement of the fiber in the powerflow hardware.
A Littlewood-Paley-Rubio de Francia inequality for bounded Vilenkin systems
Authors: Tselishchev A. S. 
Published: July 2021

Abstract
Rubio de Francia proved a one-sided Littlewood-Paley inequality for the square function constructed from an arbitrary system of disjoint intervals. Later, Osipov proved a similar inequality for Walsh systems. We prove a similar inequality for more general Vilenkin systems.	Bibliography: 11 titles.
Global and semilocal theorems on implicit and inverse functions in Banach spaces
Authors: Arutyunov A. V. , Zhukovskiy S. E. 
Published: July 2021

Abstract
We consider continuous mappings between two Banach spaces that depend on a parameter with values in a topological space. These mappings are assumed to be continuously differentiable for each value of the parameter. Under normality (regularity) assumptions of the mappings under consideration, we obtain sufficient conditions for the existence of global and semilocal implicit functions. A priori estimates for solutions are given. As an application of these results, we obtain, in particular, a theorem on extending an implicit function from a given closed set to the whole parameter space and a theorem on coincidence points of mappings.
Bibliography: 32 titles.
Inactivation of the tumor suppressor p53 by long noncoding RNA RMRP
Authors: Chen Yajie , Hao Qian , Wang Shanshan , Cao Mingming , Huang Yingdan , Weng Xiaoling , Wang Jieqiong , Zhang Zhen , He Xianghuo , Lu Hua , Zhou Xiang 
Published: July 2021

Significance
The tumor suppressor p53 prevents tumorigenesis, while inactivation of p53 promotes cancer development and drug resistance. Here, we identify that a long noncoding RNA, the RNA component of mitochondrial RNA-processing endoribonuclease (RMRP), promotes growth and proliferation of colorectal cancer cells by inhibiting p53 activity. Mechanistically, RMRP retains SNRPA1 in the nucleus, thus preventing its lysosomal degradation. The nuclear SNRPA1 then prompts MDM2-mediated p53 ubiquitination and degradation. Remarkably, RMRP expression is induced by poly (ADP-ribose) polymerase (PARP) inhibitors, a group of targeted anticancer drugs, through the transcription factor C/EBPβ. Targeting RMRP significantly enhances sensitivity of colorectal cancer cells to PARP inhibition by reactivating p53. Our study provides a possible mechanism underling tumor resistance to PARP inhibitors.