bluuebunny/crossref_metadata_2025 huggingface dataset:
Simulating fluid flow in complex porous materials by integrating the governing equations with deep-layered machines
Authors: Kamrava Serveh , Sahimi Muhammad , Tahmasebi Pejman
Published: August 2021

Fluid flow in heterogeneous porous media arises in many systems, from biological tissues to composite materials, soil, wood, and paper. With advances in instrumentations, high-resolution images of porous media can be obtained and used directly in the simulation of fluid flow. The computations are, however, highly intensive. Although machine learning (ML) algorithms have been used for predicting flow properties of porous media, they lack a rigorous, physics-based foundation and rely on correlations. We introduce an ML approach that incorporates mass conservation and the Navier–Stokes equations in its learning process. By training the algorithm to relatively limited data obtained from the solutions of the equations over a time interval, we show that the approach provides highly accurate predictions for the flow properties of porous media at all other times and spatial locations, while reducing the computation time. We also show that when the network is used for a different porous medium, it again provides very accurate predictions.
Estimating the predictive power of silent mutations on cancer classification and prognosis
Authors: Gutman Tal , Goren Guy , Efroni Omri , Tuller Tamir
Published: August 2021

In recent years it has been shown that silent mutations, in and out of the coding region, can affect gene expression and may be related to tumorigenesis and cancer cell fitness. However, the predictive ability of these mutations for cancer type diagnosis and prognosis has not been evaluated yet. In the current study, based on the analysis of 9,915 cancer genomes and approximately three million mutations, we provide a comprehensive quantitative evaluation of the predictive power of various types of silent and non-silent mutations over cancer classification and prognosis. The results indicate that silent-mutation models outperform the equivalent null models in classifying all examined cancer types and in estimating the probability of survival 10 years after the initial diagnosis. Additionally, combining both non-silent and silent mutations achieved the best classification results for 68% of the cancer types and the best survival estimation results for up to nine years after the diagnosis. Thus, silent mutations hold considerable predictive power over both cancer classification and prognosis, most likely due to their effect on gene expression. It is highly advised that silent mutations are integrated in cancer research in order to unravel the full genomic landscape of cancer and its ramifications on cancer fitness.
Cardiac sympathetic burden reflects Parkinson disease burden, regardless of high or low orthostatic blood pressure changes
Authors: Yoo Sang-Won , Kim Joong-Seok , Oh Yoon-Sang , Ryu Dong-Woo , Ha Seunggyun , Yoo Ji-Yeon , Lee Kwang-Soo
Published: August 2021

Reduced uptake of 123I-meta-iodobenzylguanidine (123I-MIBG) and orthostatic hypotension (OH) are independently associated with worse clinical outcomes of Parkinson’s disease (PD). However, their interactive influence on PD has not been studied. The role of 123I-MIBG myocardial uptake, as a biomarker of PD severity, was investigated, conditional on the mediating effects of OH. A total of 227 PD patients were enrolled. Their motor and nonmotor aspects were assessed with standardized tools. Global disease burden was estimated by averaging the scaled z-scores of the assessment tools. Every patient went through 123I-MIBG scan, and OH was evaluated with the head-up tilt-test. The mediating role of orthostatic blood pressure changes (ΔBP) on the association between cardiac sympathetic denervation and disease burden was investigated. Low heart-to-mediastinum (H/M) ratio with less than 1.78 was seen in 69.6% of the patient population, and 22.9% of patients had OH. Low H/M ratio was associated with OH, and these patients had worse disease burden than subjects with normal 123I-MIBG uptake (global composite z-score: normal 123I-MIBG vs. abnormal 123I-MIBG; −0.3 ± 0.5 vs. 0.1 ± 0.7; p < 0.001). The mediation models, controlled for age and disease duration, revealed that the delayed H/M ratio and global composite score were negatively associated, irrespective of orthostatic ΔBP. Adverse relationship between cardiac sympathetic denervation and disease burden was shown without any interference from orthostatic blood pressure fluctuations. This result suggested that extracranial cardiac markers might reflect disease burden, regardless of labile blood pressure influence.
Efficient verification of anticoncentrated quantum states
Authors: Bennink Ryan S.
Published: August 2021

I present a method for estimating the fidelity F(μ, τ) between a preparable quantum state μ and a classically specified pure target state $$\tau =\left|\tau \right\rangle \left\langle \tau \right|$$

τ
=

τ

τ

, using simple quantum circuits and on-the-fly classical calculation (or lookup) of selected amplitudes of $$\left|\tau \right\rangle$$

τ

. The method is sample efficient for anticoncentrated states (including many states that are hard to simulate classically), with approximate cost 4ϵ−2(1 − F)dpcoll where ϵ is the desired precision of the estimate, d is the dimension of the Hilbert space, and pcoll is the collision probability of the target distribution. This scaling is exponentially better than that of any method based on classical sampling. I also present a more sophisticated version of the method that uses any efficiently preparable and well-characterized quantum state as an importance sampler to further reduce the number of copies of μ needed. Though some challenges remain, this work takes a significant step toward scalable verification of complex states produced by quantum processors.
Monoclonal antibodies block transmission of genetically diverse Plasmodium falciparum strains to mosquitoes
Authors: de Jong Roos M. , Meerstein-Kessel Lisette , Da Dari F. , Nsango Sandrine , Challenger Joseph D. , van de Vegte-Bolmer Marga , van Gemert Geert-Jan , Duarte Elias , Teyssier Noam , Sauerwein Robert W. , Churcher Thomas S. , Dabire Roch K. , Morlais Isabelle , Locke Emily , Huynen Martijn A. , Bousema Teun , Jore Matthijs M.
Published: August 2021

Malaria parasite transmission to mosquitoes relies on the uptake of sexual stage parasites during a blood meal and subsequent formation of oocysts on the mosquito midgut wall. Transmission-blocking vaccines (TBVs) and monoclonal antibodies (mAbs) target sexual stage antigens to interrupt human-to-mosquito transmission and may form important tools for malaria elimination. Although most epitopes of these antigens are considered highly conserved, little is known about the impact of natural genetic diversity on the functional activity of transmission-blocking antibodies. Here we measured the efficacy of three mAbs against leading TBV candidates (Pfs48/45, Pfs25 and Pfs230) in transmission assays with parasites from naturally infected donors compared to their efficacy against the strain they were raised against (NF54). Transmission-reducing activity (TRA) was measured as reduction in mean oocyst intensity. mAb 45.1 (α-Pfs48/45) and mAb 4B7 (α-Pfs25) reduced transmission of field parasites from almost all donors with IC80values similar to NF54. Sequencing of oocysts that survived high mAb concentrations did not suggest enrichment of escape genotypes. mAb 2A2 (α-Pfs230) only reduced transmission of parasites from a minority of the donors, suggesting that it targets a non-conserved epitope. Using six laboratory-adapted strains, we revealed that mutations in one Pfs230 domain correlate with mAb gamete surface binding and functional TRA. Our findings demonstrate that, despite the conserved nature of sexual stage antigens, minor sequence variation can significantly impact the efficacy of transmission-blocking mAbs. Since mAb 45.1 shows high potency against genetically diverse strains, our findings support its further clinical development and may inform Pfs48/45 vaccine design.
Oral vaccination stimulates neutrophil functionality and exerts protection in a Mycobacterium avium subsp. paratuberculosis infection model
Authors: Ladero-Auñon Iraia , Molina Elena , Oyanguren Maddi , Barriales Diego , Fuertes Miguel , Sevilla Iker A. , Luo Lucy , Arrazuria Rakel , De Buck Jeroen , Anguita Juan , Elguezabal Natalia
Published: August 2021

Mycobacterium avium subsp. paratuberculosis (Map) causes paratuberculosis (PTB), a granulomatous enteritis in ruminants that exerts high economic impact on the dairy industry worldwide. Current vaccines have shown to be cost-effective against Map and in some cases confer beneficial non-specific effects against other pathogens suggesting the existence of trained immunity. Although Map infection is mainly transmitted by the fecal-oral route, oral vaccination has not been deeply studied. Therefore, the aim of this study was to compare the oral route with a set of mycobacterial and non-mycobacterial vaccines with a subcutaneously administered commercially available vaccine. Training effects on polymorphonuclear neutrophils (PMNs) and homologous and heterologous in vivo protection against Map were investigated in the rabbit infection model. Oral vaccination with inactivated or live vaccines was able to activate mucosal immunity as seen by elevation of serum IgA and the expression of IL4 in peripheral blood mononuclear cells (PBMCs). In addition, peripheral PMN phagocytosis against Map was enhanced by vaccination and extracellular trap release against Map and non-related pathogens was modified by both, vaccination and Map-challenge, indicating trained immunity. Finally, PBMCs from vaccinated animals stimulated in vitro with Map antigens showed a rapid innate activation cytokine profile. In conclusion, our data show that oral vaccination against PTB can stimulate neutrophil activity and both innate and adaptive immune responses that correlate with protection.
Combinatorial optimization by weight annealing in memristive hopfield networks
Authors: Fahimi Z. , Mahmoodi M. R. , Nili H. , Polishchuk Valentin , Strukov D. B.
Published: August 2021

The increasing utility of specialized circuits and growing applications of optimization call for the development of efficient hardware accelerator for solving optimization problems. Hopfield neural network is a promising approach for solving combinatorial optimization problems due to the recent demonstrations of efficient mixed-signal implementation based on emerging non-volatile memory devices. Such mixed-signal accelerators also enable very efficient implementation of various annealing techniques, which are essential for finding optimal solutions. Here we propose a “weight annealing” approach, whose main idea is to ease convergence to the global minima by keeping the network close to its ground state. This is achieved by initially setting all synaptic weights to zero, thus ensuring a quick transition of the Hopfield network to its trivial global minima state and then gradually introducing weights during the annealing process. The extensive numerical simulations show that our approach leads to a better, on average, solutions for several representative combinatorial problems compared to prior Hopfield neural network solvers with chaotic or stochastic annealing. As a proof of concept, a 13-node graph partitioning problem and a 7-node maximum-weight independent set problem are solved experimentally using mixed-signal circuits based on, correspondingly, a 20 × 20 analog-grade TiO2 memristive crossbar and a 12 × 10 eFlash memory array.
Genetic engineering of Pseudomonas chlororaphis Lzh-T5 to enhance production of trans-2,3-dihydro-3-hydroxyanthranilic acid
Authors: Liu Kaiquan , Li Ling , Yao Wentao , Wang Wei , Huang Yujie , Wang Ruiming , Li Piwu
Published: August 2021

Trans-2,3-dihydro-3-hydroxyanthranilic acid (DHHA) is a cyclic β-amino acid used for the synthesis of non-natural peptides and chiral materials. And it is an intermediate product of phenazine production in Pseudomonas spp. Lzh-T5 is a P. chlororaphis strain isolated from tomato rhizosphere found in China. It can synthesize three antifungal phenazine compounds. Disruption the phzF gene of P. chlororaphis Lzh-T5 results in DHHA accumulation. Several strategies were used to improve production of DHHA: enhancing the shikimate pathway by overexpression, knocking out negative regulatory genes, and adding metal ions to the medium. In this study, three regulatory genes (psrA, pykF, and rpeA) were disrupted in the genome of P. chlororaphis Lzh-T5, yielding 5.52 g/L of DHHA. When six key genes selected from the shikimate, pentose phosphate, and gluconeogenesis pathways were overexpressed, the yield of DHHA increased to 7.89 g/L. Lastly, a different concentration of Fe3+ was added to the medium for DHHA fermentation. This genetically engineered strain increased the DHHA production to 10.45 g/L. According to our result, P. chlororaphis Lzh-T5 could be modified as a microbial factory to produce DHHA. This study laid a good foundation for the future industrial production and application of DHHA.
High-temperature superconductor of sodalite-like clathrate hafnium hexahydride
Authors: Tsuppayakorn-aek Prutthipong , Phaisangittisakul Nakorn , Ahuja Rajeev , Bovornratanaraks Thiti
Published: August 2021

Hafnium hydrogen compounds have recently become the vibrant materials for structural prediction at high pressure, from their high potential candidate for high-temperature superconductors. In this work, we predict $$\hbox {HfH}_{6}$$

HfH
6

by exploiting the evolutionary searching. A high-pressure phase adopts a sodalite-like clathrate structure, showing the body-centered cubic structure with a space group of $$Im\bar{3}m$$

I
m

3

¯

m

. The first-principles calculations have been used, including the zero-point energy, to investigate the probable structures up to 600 GPa, and find that the $$Im\bar{3}m$$

I
m

3

¯

m

structure is thermodynamically and dynamically stable. This remarkable result of the $$Im\bar{3}m$$

I
m

3

¯

m

structure shows the van Hove singularity at the Fermi level by determining the density of states. We calculate a superconducting transition temperature ($$T_{c}$$

T
c

) using Allen-Dynes equation and demonstrated that it exhibits superconductivity under high pressure with relatively high-$$T_{c}$$

T
c

of 132 K.
Probabilistic nucleation governs time, amount, and location of mineral precipitation and geometry evolution in the porous medium
Authors: Nooraiepour Mohammad , Masoudi Mohammad , Hellevang Helge
Published: August 2021

One important unresolved question in reactive transport is how pore-scale processes can be upscaled and how predictions can be made on the mutual effect of chemical processes and fluid flow in the porous medium. It is paramount to predict the location of mineral precipitation besides their amount for understanding the fate of transport properties. However, current models and simulation approaches fail to predict precisely where crystals will nucleate and grow in the spatiotemporal domain. We present a new mathematical model for probabilistic mineral nucleation and precipitation. A Lattice Boltzmann implementation of the two-dimensional mineral surface was developed to evaluate geometry evolution when probabilistic nucleation criterion is incorporated. To provide high-resolution surface information on mineral precipitation, growth, and distribution, we conducted a total of 27 calcium carbonate synthesis experiments in the laboratory. The results indicate that nucleation events as precursors determine the location and timing of crystal precipitation. It is shown that reaction rate has primary control over covering the substrate with nuclei and, subsequently, solid-phase accumulation. The work provides insight into the spatiotemporal evolution of porous media by suggesting probabilistic and deterministic domains for studying reactive transport processes. We indicate in which length- and time-scales it is essential to incorporate probabilistic nucleation for valid predictions.
Mapping gene and gene pathways associated with coronary artery disease: a CARDIoGRAM exome and multi-ancestry UK biobank analysis
Authors: Hariharan Praveen , Dupuis Josée
Published: August 2021

Coronary artery disease (CAD) genome-wide association studies typically focus on single nucleotide variants (SNVs), and many potentially associated SNVs fail to reach the GWAS significance threshold. We performed gene and pathway-based association (GBA) tests on publicly available Coronary ARtery DIsease Genome wide Replication and Meta-analysis consortium Exome (n = 120,575) and multi ancestry pan UK Biobank study (n = 442,574) summary data using versatile gene-based association study (VEGAS2) and Multi-marker analysis of genomic annotation (MAGMA) to identify novel genes and pathways associated with CAD. We included only exonic SNVs and excluded regulatory regions. VEGAS2 and MAGMA ranked genes and pathways based on aggregated SNV test statistics. We used Bonferroni corrected gene and pathway significance threshold at 3.0 × 10–6 and 1.0 × 10–5, respectively. We also report the top one percent of ranked genes and pathways. We identified 17 top enriched genes with four genes (PCSK9, FAM177, LPL, ARGEF26), reaching statistical significance (p ≤ 3.0 × 10–6) using both GBA tests in two GWAS studies. In addition, our analyses identified ten genes (DUSP13, KCNJ11, CD300LF/RAB37, SLCO1B1, LRRFIP1, QSER1, UBR2, MOB3C, MST1R, and ABCC8) with previously unreported associations with CAD, although none of the single SNV associations within the genes were genome-wide significant. Among the top 1% non-lipid pathways, we detected pathways regulating coagulation, inflammation, neuronal aging, and wound healing.
Cross reactivity of neutralizing antibodies to the encephalitic California Serogroup orthobunyaviruses varies by virus and genetic relatedness
Authors: Evans Alyssa B. , Peterson Karin E.
Published: August 2021

The California Serogroup (CSG) of Orthobunyaviruses comprises several viruses capable of causing neuroinvasive disease in humans, including La Crosse (LACV), Snowshoe Hare (SSHV), Tahyna (TAHV), Jamestown Canyon (JCV), and Inkoo (INKV) viruses. Diagnosis of specific CSG viruses is complicated by the high degree of antibody cross-reactivity between them, with laboratory standards requiring a fourfold higher titer of neutralizating antibody (NAb) activity to positively identify the etiologic virus. To help elucidate NAb relationships between neuroinvasive CSG viruses, we directly compared the cross-reactivity of NAb between LACV, SSHV, TAHV, JCV, and INKV. Mice were inoculated with individual viruses and the NAb activity of plasma samples was compared by plaque reduction neutralization tests against all five viruses. Overall, the results from these studies show that the CSG viruses induced high levels of NAb against the inoculum virus, and differing amounts of cross-reactive NAb against heterologous viruses. LACV, SSHV, and INKV elicited the highest amount of cross-reactive NAb. Interestingly, a fourfold difference in NAb titer between the inoculum virus and the other CSG viruses was not always observed. Thus, NAb titers, which are the gold-standard for diagnosing the etiologic agent for viral encephalitis, may not clearly differentiate between different CSG viruses.
Reduced order modelling and experimental validation of a MEMS gyroscope test-structure exhibiting 1:2 internal resonance
Authors: Gobat Giorgio , Zega Valentina , Fedeli Patrick , Guerinoni Luca , Touzé Cyril , Frangi Attilio
Published: August 2021

Micro-Electro-Mechanical Systems revolutionized the consumer market for their small dimensions, high performances and low costs. In recent years, the evolution of the Internet of Things is posing new challenges to MEMS designers that have to deal with complex multiphysics systems experiencing highly nonlinear dynamic responses. To be able to simulate a priori and in real-time the behavior of such systems it is thus becoming mandatory to understand the sources of nonlinearities and avoid them when harmful or exploit them for the design of innovative devices. In this work, we present the first numerical tool able to estimate a priori and in real-time the complex nonlinear responses of MEMS devices without resorting to simplified theories. Moreover, the proposed tool predicts different working conditions without the need of ad-hoc calibration procedures. It consists in a nonlinear Model Order Reduction Technique based on the Implicit Static Condensation that allows to condense the high fidelity FEM models into few degrees of freedom, thus greatly speeding-up the solution phase and improving the design process of MEMS devices. In particular, the 1:2 internal resonance experienced in a MEMS gyroscope test-structure fabricated with a commercial process is numerically investigated and an excellent agreement with experiments is found.
Multimorbidity prediction using link prediction
Authors: Aziz Furqan , Cardoso Victor Roth , Bravo-Merodio Laura , Russ Dominic , Pendleton Samantha C. , Williams John A. , Acharjee Animesh , Gkoutos Georgios V.
Published: August 2021

Multimorbidity, frequently associated with aging, can be operationally defined as the presence of two or more chronic conditions. Predicting the likelihood of a patient with multimorbidity to develop a further particular disease in the future is one of the key challenges in multimorbidity research. In this paper we are using a network-based approach to analyze multimorbidity data and develop methods for predicting diseases that a patient is likely to develop. The multimorbidity data is represented using a temporal bipartite network whose nodes represent patients and diseases and a link between these nodes indicates that the patient has been diagnosed with the disease. Disease prediction then is reduced to a problem of predicting those missing links in the network that are likely to appear in the future. We develop a novel link prediction method for static bipartite network and validate the performance of the method on benchmark datasets. By using a probabilistic framework, we then report on the development of a method for predicting future links in the network, where links are labelled with a time-stamp. We apply the proposed method to three different multimorbidity datasets and report its performance measured by different performance metrics including AUC, Precision, Recall, and F-Score.
Incident stroke in patients with Alzheimer’s disease: systematic review and meta-analysis
Authors: Pinho João , Quintas-Neves Miguel , Dogan Imis , Reetz Kathrin , Reich Arno , Costa Ana Sofia
Published: August 2021

Vascular mechanisms are increasingly recognized in the pathophysiology of Alzheimer’s disease (AD), but less is known about the occurrence of stroke in AD patients. We aimed to quantify the risk of stroke in patients with AD and compare the incidence rates (IR) of stroke in individuals without AD. Systematic search of Embase and MEDLINE between 1970 and 2020. Inclusion criteria: reports with ≥ 50 patients with non-familial AD, which reported the occurrence of stroke (all types) and/or ischemic stroke and/or intracerebral hemorrhage (ICH) during follow-up. Meta-analyses of pooled data using random-effects model were performed. IR were calculated for each study. Incidence rate ratios (IRR) were calculated for studies presenting a control-group without AD. Among 5109 retrieved studies, 29 (0.6%) fulfilled the inclusion criteria, reporting a total of 61,824 AD patients. In AD patients the IR were 15.4/1000 person-years for stroke (all types), 13.0/1000 person-years for ischemic stroke and 3.4/1000 person-years for ICH. When compared to controls without AD, incidence rate for ICH in AD patients was significantly higher (IRR = 1.67, 95%CI 1.43–1.96), but similar for ischemic stroke. Incident stroke is not a rare event in AD population. AD is associated with an increased risk of intracerebral hemorrhage which warrants further clarification.
Adequacy of antibiotic prophylaxis and incidence of surgical site infections in neck surgery
Authors: Alonso-García M. , Toledano-Muñoz A. , Aparicio-Fernández J. M. , De-la-Rosa-Astacio F. M. , Rodríguez-Villar D. , Gil-de-Miguel A. , Durán-Poveda M. , Rodríguez-Caravaca G.
Published: August 2021

Health care-related infections are frequent and among them surgical site infection (SSI) are the most frequent in hospitals. The objective was to evaluate the adequacy of antibiotic prophylaxis in patients undergoing neck surgery and its relationship with the incidence of surgical site infection (SSI). Prospective cohort study. The adequacy of antibiotic prophylaxis in patients undergoing neck surgery was evaluated. Antibiotic prophylaxis was considered adequate when it conformed to all items of the protocol (antibiotic used, time of administration, administration route, dose and duration). The cumulative incidence of SSI was calculated, and the relationship between SSI and antibiotic prophylaxis adequacy was determined using adjusted relative risk (RR). Antibiotic prophylaxis was administered in 63 patients and was adequate in 85.7% (95% CI 75.0–92.3) of them. The cumulative incidence of SSI was 6.4% (95% CI 3.4–11.8). There was no significant relationship between antibiotic prophylaxis inadequacy and the incidence of SSI (RR = 2.4, 95% CI 0.6–10.6). Adequacy of antibiotic prophylaxis was high and it did not affect the incidence of SSIs.
Prognostic role of docetaxel-induced suppression of free testosterone serum levels in metastatic prostate cancer patients
Authors: Kappler Paula , Morgan Michael A. , Ivanyi Philipp , Brunotte Stefan J. , Ganser Arnold , Reuter Christoph W. M.
Published: August 2021

To date, only few data concerning the biologically active, free form of testosterone (FT) are available in metastatic prostate cancer (mPC) and the impact of FT on disease, therapy and outcome is largely unknown. We retrospectively studied the effect of docetaxel on FT and total testosterone (TT) serum levels in 67 mPC patients monitored between April 2008 and November 2020. FT and TT levels were measured before and weekly during therapy. The primary endpoint was overall survival (OS). Secondary endpoints were prostate-specific antigen response and radiographic response (PSAR, RR), progression-free survival (PFS), FT/TT levels and safety. Median FT and TT serum levels were completely suppressed to below the detection limit during docetaxel treatment (FT: from 0.32 to < 0.18 pg/mL and TT: from 0.12 to < 0.05 ng/mL, respectively). Multivariate Cox regression analyses identified requirement of non-narcotics, PSAR, complete FT suppression and FT nadir values < 0.18 pg/mL as independent parameters for PFS. Prior androgen-receptor targeted therapy (ART), soft tissue metastasis and complete FT suppression were independent prognostic factors for OS. FT was not predictive for treatment outcome in mPC patients with a history of ART.
Integrated computational and experimental pipeline for quantifying local cell–matrix interactions
Authors: Xiao Hugh , Nguyen Ryan Y. , LaRanger Ryan , Herzog Erica L. , Mak Michael
Published: August 2021

Cellular interactions with the extracellular matrix (ECM) play a key role in modulating biological processes. While studies have identified key molecular factors of these interactions, the mechanical regulation associated with these interactions is not well characterized. To address this, we present an image analysis platform to analyze time-dependent dynamics observed in lung fibroblasts embedded in a 3D collagen matrix. Combining drug studies with quantitative analysis of cell–matrix interactions, our results are able to provide cellular level quantitative insights for mechanical and biophysical phenomena relevant to cell-ECM interactions. This system overall represents an initial pipeline for understanding cell mechanics in a 3D collagen gel and their implications in a physiologically relevant context.
Fitness consequences of biochemical adaptation in Drosophila melanogaster populations under simultaneous selection for faster pre-adult development and extended lifespan
Authors: Sharma Khushboo , Shakarad Mallikarjun N.
Published: August 2021

In holometabolous insects like Drosophila melanogaster, critical size is an important time point during larval life, for irreversible commitment to metamorphosis. Here, we studied the impact of restricted growth duration in terms of selection for faster pre-adult development in Drosophila melanogaster populations which resulted in the evolution of reduced critical size on adult life history traits. Selection for faster pre-adult development resulted in biochemical adaptation in larval physiology with no compromise in major biomolecules at critical size time point. The flies from the selected populations seem to not only commit to metamorphosis on the attainment of critical size but also seem to channelize resources to reproduction as indicated by similar life-time fecundity of CS and NS flies from selected populations, while the Control CS flies significantly lower life-time fecundity compared to Control NS flies. The flies from selected populations seem to achieve longevity comparable to control flies despite being significantly smaller in size-thus resource constrained due to faster pre-adult development.
Manual kidney stone size measurements in computed tomography are most accurate using multiplanar image reformatations and bone window settings
Authors: Reimer Robert Peter , Klein Konstantin , Rinneburger Miriam , Zopfs David , Lennartz Simon , Salem Johannes , Heidenreich Axel , Maintz David , Haneder Stefan , Große Hokamp Nils
Published: August 2021

Computed tomography in suspected urolithiasis provides information about the presence, location and size of stones. Particularly stone size is a key parameter in treatment decision; however, data on impact of reformatation and measurement strategies is sparse. This study aimed to investigate the influence of different image reformatations, slice thicknesses and window settings on stone size measurements. Reference stone sizes of 47 kidney stones representative for clinically encountered compositions were measured manually using a digital caliper (Man-M). Afterwards stones were placed in a 3D-printed, semi-anthropomorphic phantom, and scanned using a low dose protocol (CTDIvol 2 mGy). Images were reconstructed using hybrid-iterative and model-based iterative reconstruction algorithms (HIR, MBIR) with different slice thicknesses. Two independent readers measured largest stone diameter on axial (2 mm and 5 mm) and multiplanar reformatations (based upon 0.67 mm reconstructions) using different window settings (soft-tissue and bone). Statistics were conducted using ANOVA ± correction for multiple comparisons. Overall stone size in CT was underestimated compared to Man-M (8.8 ± 2.9 vs. 7.7 ± 2.7 mm, p < 0.05), yet closely correlated (r = 0.70). Reconstruction algorithm and slice thickness did not significantly impact measurements (p > 0.05), while image reformatations and window settings did (p < 0.05). CT measurements using multiplanar reformatation with a bone window setting showed closest agreement with Man-M (8.7 ± 3.1 vs. 8.8 ± 2.9 mm, p < 0.05, r = 0.83). Manual CT-based stone size measurements are most accurate using multiplanar image reformatation with a bone window setting, while measurements on axial planes with different slice thicknesses underestimate true stone size. Therefore, this procedure is recommended when impacting treatment decision.
Effect of antibiotic treatment on Oxalobacter formigenes colonization of the gut microbiome and urinary oxalate excretion
Authors: Nazzal Lama , Francois Fritz , Henderson Nora , Liu Menghan , Li Huilin , Koh Hyunwook , Wang Chan , Gao Zhan , Perez Guillermo Perez , Asplin John R. , Goldfarb David S , Blaser Martin J
Published: August 2021

The incidence of kidney stones is increasing in the US population. Oxalate, a major factor for stone formation, is degraded by gut bacteria reducing its intestinal absorption. Intestinal O. formigenes colonization has been associated with a lower risk for recurrent kidney stones in humans. In the current study, we used a clinical trial of the eradication of Helicobacter pylori to assess the effects of an antibiotic course on O. formigenes colonization, urine electrolytes, and the composition of the intestinal microbiome. Of 69 healthy adult subjects recruited, 19 received antibiotics for H. pylori eradication, while 46 were followed as controls. Serial fecal samples were examined for O. formigenes presence and microbiota characteristics. Urine, collected serially fasting and following a standard meal, was tested for oxalate and electrolyte concentrations. O. formigenes prevalence was 50%. Colonization was significantly and persistently suppressed in antibiotic-exposed subjects but remained stable in controls. Urinary pH increased after antibiotics, but urinary oxalate did not differ between the control and treatment groups. In subjects not on antibiotics, the O. formigenes-positive samples had higher alpha-diversity and significantly differed in Beta-diversity from the O. formigenes-negative samples. Specific taxa varied in abundance in relation to urinary oxalate levels. These studies identified significant antibiotic effects on O. formigenes colonization and urinary electrolytes and showed that overall microbiome structure differed in subjects according to O. formigenes presence. Identifying a consortium of bacterial taxa associated with urinary oxalate may provide clues for the primary prevention of kidney stones in healthy adults.
Aerosol, chemical and physical properties of dry powder synthetic lung surfactant for noninvasive treatment of neonatal respiratory distress syndrome
Authors: Walther Frans J. , Chan Holly , Smith Jacob R. , Tauber Mike , Waring Alan J.
Published: August 2021

Inhalation of dry powder synthetic lung surfactant may assist spontaneous breathing by providing noninvasive surfactant therapy for premature infants supported with nasal continuous positive airway pressure. Surfactant was formulated using spray-drying with different phospholipid compositions (70 or 80 total weight% and 7:3 or 4:1 DPPC:POPG ratios), a surfactant protein B peptide analog (KL4, Super Mini-B, or B-YL), and Lactose or Trehalose as excipient. KL4 surfactant underperformed on initial adsorption and surface activity at captive bubble surfactometry. Spray-drying had no effect on the chemical composition of Super Mini-B and B-YL peptides and surfactant with these peptides had excellent surface activity with particle sizes and fine particle fractions that were well within the margins for respiratory particles and similar solid-state properties. Prolonged exposure of the dry powder surfactants with lactose as excipient to 40 °C and 75% humidity negatively affected hysteresis during dynamic cycling in the captive bubble surfactometer. Dry powder synthetic lung surfactants with 70% phospholipids (DPPC and POPG at a 7:3 ratio), 25% trehalose and 3% of SMB or B-YL showed excellent surface activity and good short-term stability, thereby qualifying them for potential clinical use in premature infants.
Machine learning using clinical data at baseline predicts the efficacy of vedolizumab at week 22 in patients with ulcerative colitis
Authors: Miyoshi Jun , Maeda Tsubasa , Matsuoka Katsuyoshi , Saito Daisuke , Miyoshi Sawako , Matsuura Minoru , Okamoto Susumu , Tamura Satoshi , Hisamatsu Tadakazu
Published: August 2021

Predicting the response of patients with ulcerative colitis (UC) to a biologic such as vedolizumab (VDZ) before administration is an unmet need for optimizing individual patient treatment. We hypothesized that the machine-learning approach with daily clinical information can be a new, promising strategy for developing a drug-efficacy prediction tool. Random forest with grid search and cross-validation was employed in Cohort 1 to determine the contribution of clinical features at baseline (week 0) to steroid-free clinical remission (SFCR) with VDZ at week 22. Among 49 clinical features including sex, age, height, body weight, BMI, disease duration/phenotype, treatment history, clinical activity, endoscopic activity, and blood test items, the top eight features (partial Mayo score, MCH, BMI, BUN, concomitant use of AZA, lymphocyte fraction, height, and CRP) were selected for logistic regression to develop a prediction model for SFCR at week 22. In the validation using the external Cohort 2, the positive and negative predictive values of the prediction model were 54.5% and 92.3%, respectively. The prediction tool appeared useful for identifying patients with UC who would not achieve SFCR at week 22 during VDZ therapy. This study provides a proof-of-concept that machine learning using real-world data could permit personalized treatment for UC.
Circulating tumor cell heterogeneity in neuroendocrine prostate cancer by single cell copy number analysis
Authors: Conteduca Vincenza , Ku Sheng-Yu , Fernandez Luisa , Dago-Rodriquez Angel , Lee Jerry , Jendrisak Adam , Slade Megan , Gilbertson Cole , Manohar Jyothi , Sigouros Michael , Wang Yipeng , Dittamore Ryan , Wenstrup Rick , Mosquera Juan Miguel , Schonhoft Joseph D. , Beltran Himisha
Published: August 2021

Neuroendocrine prostate cancer is an aggressive variant of prostate cancer that may arise de novo or develop from pre-existing prostate adenocarcinoma as a mechanism of treatment resistance. The combined loss of tumor suppressors RB1, TP53, and PTEN are frequent in NEPC but also present in a subset of prostate adenocarcinomas. Most clinical and preclinical studies support a trans-differentiation process, whereby NEPC arises clonally from a prostate adenocarcinoma precursor during the course of treatment resistance. Here we highlight a case of NEPC with significant intra-patient heterogeneity observed across metastases. We further demonstrate how single-cell genomic analysis of circulating tumor cells combined with a phenotypic evaluation of cellular diversity can be considered as a window into tumor heterogeneity in patients with advanced prostate cancer.
Prediction and verification of the AD-FTLD common pathomechanism based on dynamic molecular network analysis
Authors: Jin Meihua , Jin Xiaocen , Homma Hidenori , Fujita Kyota , Tanaka Hikari , Murayama Shigeo , Akatsu Hiroyasu , Tagawa Kazuhiko , Okazawa Hitoshi
Published: August 2021

Multiple gene mutations cause familial frontotemporal lobar degeneration (FTLD) while no single gene mutations exists in sporadic FTLD. Various proteins aggregate in variable regions of the brain, leading to multiple pathological and clinical prototypes. The heterogeneity of FTLD could be one of the reasons preventing development of disease-modifying therapy. We newly develop a mathematical method to analyze chronological changes of PPI networks with sequential big data from comprehensive phosphoproteome of four FTLD knock-in (KI) mouse models (PGRNR504X-KI, TDP43N267S-KI, VCPT262A-KI and CHMP2BQ165X-KI mice) together with four transgenic mouse models of Alzheimer’s disease (AD) and with APPKM670/671NL-KI mice at multiple time points. The new method reveals the common core pathological network across FTLD and AD, which is shared by mouse models and human postmortem brains. Based on the prediction, we performed therapeutic intervention of the FTLD models, and confirmed amelioration of pathologies and symptoms of four FTLD mouse models by interruption of the core molecule HMGB1, verifying the new mathematical method to predict dynamic molecular networks.
Plant single-cell solutions for energy and the environment
Authors: Cole Benjamin , Bergmann Dominique , Blaby-Haas Crysten E. , Blaby Ian K. , Bouchard Kristofer E. , Brady Siobhan M. , Ciobanu Doina , Coleman-Derr Devin , Leiboff Samuel , Mortimer Jenny C. , Nobori Tatsuya , Rhee Seung Y. , Schmutz Jeremy , Simmons Blake A. , Singh Anup K. , Sinha Neelima , Vogel John P. , O’Malley Ronan C. , Visel Axel , Dickel Diane E.
Published: August 2021

Progress in sequencing, microfluidics, and analysis strategies has revolutionized the granularity at which multicellular organisms can be studied. In particular, single-cell transcriptomics has led to fundamental new insights into animal biology, such as the discovery of new cell types and cell type-specific disease processes. However, the application of single-cell approaches to plants, fungi, algae, or bacteria (environmental organisms) has been far more limited, largely due to the challenges posed by polysaccharide walls surrounding these species’ cells. In this perspective, we discuss opportunities afforded by single-cell technologies for energy and environmental science and grand challenges that must be tackled to apply these approaches to plants, fungi and algae. We highlight the need to develop better and more comprehensive single-cell technologies, analysis and visualization tools, and tissue preparation methods. We advocate for the creation of a centralized, open-access database to house plant single-cell data. Finally, we consider how such efforts should balance the need for deep characterization of select model species while still capturing the diversity in the plant kingdom. Investments into the development of methods, their application to relevant species, and the creation of resources to support data dissemination will enable groundbreaking insights to propel energy and environmental science forward.
Spatial and temporal scales of variability for indoor air constituents
Authors: Lakey Pascale S. J. , Won Youngbo , Shaw David , Østerstrøm Freja F. , Mattila James , Reidy Emily , Bottorff Brandon , Rosales Colleen , Wang Chen , Ampollini Laura , Zhou Shan , Novoselac Atila , Kahan Tara F. , DeCarlo Peter F. , Abbatt Jonathan P. D. , Stevens Philip S. , Farmer Delphine K. , Carslaw Nicola , Rim Donghyun , Shiraiwa Manabu
Published: August 2021

Historically air constituents have been assumed to be well mixed in indoor environments, with single point measurements and box modeling representing a room or a house. Here we demonstrate that this fundamental assumption needs to be revisited through advanced model simulations and extensive measurements of bleach cleaning. We show that inorganic chlorinated products, such as hypochlorous acid and chloramines generated via multiphase reactions, exhibit spatial and vertical concentration gradients in a room, with short-lived ⋅OH radicals confined to sunlit zones, close to windows. Spatial and temporal scales of indoor constituents are modulated by rates of chemical reactions, surface interactions and building ventilation, providing critical insights for better assessments of human exposure to hazardous pollutants, as well as the transport of indoor chemicals outdoors.
Site-specific interrogation of an ionic chiral fragment during photolysis using an X-ray free-electron laser
Authors: Ilchen Markus , Schmidt Philipp , Novikovskiy Nikolay M. , Hartmann Gregor , Rupprecht Patrick , Coffee Ryan N. , Ehresmann Arno , Galler Andreas , Hartmann Nick , Helml Wolfram , Huang Zhirong , Inhester Ludger , Lutman Alberto A. , MacArthur James P. , Maxwell Timothy , Meyer Michael , Music Valerija , Nuhn Heinz-Dieter , Osipov Timur , Ray Dipanwita , Wolf Thomas J. A. , Bari Sadia , Walter Peter , Li Zheng , Moeller Stefan , Knie André , Demekhin Philipp V.
Published: August 2021

Short-wavelength free-electron lasers with their ultrashort pulses at high intensities have originated new approaches for tracking molecular dynamics from the vista of specific sites. X-ray pump X-ray probe schemes even allow to address individual atomic constituents with a ‘trigger’-event that preludes the subsequent molecular dynamics while being able to selectively probe the evolving structure with a time-delayed second X-ray pulse. Here, we use a linearly polarized X-ray photon to trigger the photolysis of a prototypical chiral molecule, namely trifluoromethyloxirane (C3H3F3O), at the fluorine K-edge at around 700 eV. The created fluorine-containing fragments are then probed by a second, circularly polarized X-ray pulse of higher photon energy in order to investigate the chemically shifted inner-shell electrons of the ionic mother-fragment for their stereochemical sensitivity. We experimentally demonstrate and theoretically support how two-color X-ray pump X-ray probe experiments with polarization control enable XFELs as tools for chiral recognition.
Anomalous spin relaxation in graphene nanostructures on the high temperature annealed surface of hydrogenated diamond nanoparticles
Authors: Joly V. L. Joseph , Takai Kazuyuki , Kiguchi Manabu , Komatsu Naoki , Enoki Toshiaki
Published: August 2021

The magnetization relaxation rate of graphene nanostructures created on the surface of hydrogenated nanodiamond by high temperature annealing is explained in terms of a combination of the non-Arrhenius thermal process and the tunneling process.
Effects of surface contamination on the interfacial properties of CO2/water/calcite systems
Authors: Thi Bao Le Tran , Divine-Ayela Candice , Striolo Alberto , Cole David R.
Published: August 2021

Understanding the wetting properties of reservoir rocks can be of great benefit for advanced applications such as the effective trapping and geological storage of CO2.
DPD simulations on mixed polymeric DOX-loaded micelles assembled from PCL-SS-PPEGMA/PDEA–PPEGMA and their dual pH/reduction-responsive release
Authors: Yang Zexiong , Zhao Haiqian , Wang Delin , Yin Li , Cai Kenxiang , Lin Zehua , Chen Tao , Yang Chufen
Published: August 2021

The dual reduction/pH-responsive DOX release mechanism was revealed by DPD mesoscopic simulations with a dedicated disulfide bond-breaking script.
A valence balancing rule for the design of bimetallic phosphides targeting high thermoelectric performance
Authors: Liu Qinxi , Liu Yinqiao , Xing Jianpei , Jiang Xue , Zhao Jijun
Published: August 2021

A class of stable bimetallic phosphides have designed to obtain high thermoelectric performance.
Local structuring of diketopyrrolopyrrole (DPP)-based oligomers from molecular dynamics simulations
Authors: Reisjalali Maryam , Burgos-Mármol J. Javier , Manurung Rex , Troisi Alessandro
Published: August 2021

Molecular dynamics simulations show how the aggregation of polymer chains containing diketopyrrolopyrrole is modulated by the chemical structure of the conjugated backbone.
Electrochemical oxidative synthesis of 2-benzoylquinazolin-4(3H)-one via C(sp3)–H amination under metal-free conditions
Authors: Hu Yongzhi , Ma Xinhua , Hou Huiqing , Sun Weiming , Tu Shuqing , Wu Mei , Lin Rongkun , Xu Xiuzhi , Ke Fang
Published: August 2021

An electrochemically induced C(sp3)–H amination of 2-aminobenzamides with ketones using TBAI as a catalyst was developed, and provided 2-benzoylquinazolin-4(3H)-ones under metal-free conditions.
Ru nanoparticles on a Cs-loaded MgO superbase as highly efficient catalysts for ammonia synthesis
Authors: Liu Lin , Zhang Xilun , Ju Xiaohua , Feng Ji , Wang Jiemin , Chen Ping
Published: August 2021

Ru nanoparticles supported on Cs-loaded MgO exhibit excellent catalytic activity and stability in the catalytic ammonia synthesis reaction due to the abundant surface superbasic sites.
Phenanthroimidazole-based bipolar carbazoles featuring cyano substituents to realize efficient deep-blue electroluminescence with an external quantum efficiency of nearly 6%
Authors: Sharma Anuj , Thomas K. R. Justin , Nagar Mangey Ram , Jou Jwo-Huei
Published: August 2021

Organic emitters comprising carbazole and phenanthroimidazole with tunable optical and electronic properties due to the position and number of cyano substituents on the carbazole core are described.
It takes two to tango: synthesis of cytotoxic quinones containing two redox active centers with potential antitumor activity
Authors: Lima Daisy J. B. , Almeida Renata G. , Jardim Guilherme A. M. , Barbosa Breno P. A. , Santos Augusto C. C. , Valença Wagner O. , Scheide Marcos R. , Gatto Claudia C. , de Carvalho Guilherme G. C. , Costa Pedro M. S. , Pessoa Claudia , Pereira Cynthia L. M. , Jacob Claus , Braga Antonio L. , da Silva Júnior Eufrânio N.
Published: August 2021

Quinone-based frameworks with antitumor activities were described. We identified compounds with IC50 values below 0.5 μM in cancer cells lines with significantly lower cytotoxicity in the control cell line L929.