bluuebunny/crossref_metadata_2025 huggingface dataset:
Crystal structure of tofacitinib dihydrogen citrate (Xeljanz®), (C16H21N6O)(H2C6H5O7)
Authors: Kaduk James A. , Gindhart Amy M. , Blanton Thomas N.
Published: February 2021

The crystal structure of tofacitinib dihydrogen citrate (tofacitinib citrate) has been solved and refined using synchrotron X-ray powder diffraction data, and optimized using density functional techniques. Tofacitinib dihydrogen citrate crystallizes in space group P212121 (#19) with a = 5.91113(1), b = 12.93131(3), c = 30.43499(7) Å, V = 2326.411(6) Å3, and Z = 4. The crystal structure consists of corrugated layers perpendicular to the c-axis. Within the layers, cation⋯anion and anion⋯anion hydrogen bonds link the fragments into a two-dimensional network parallel to the ab-plane. Between the layers, there are only van der Waals contacts. A terminal carboxylic acid group in the citrate anion forms a strong charge-assisted hydrogen bond to the ionized central carboxylate group. The other carboxylic acid acts as a donor to the carbonyl group of the cation. The citrate hydroxy group forms an intramolecular charge-assisted hydrogen bond to the ionized central carboxylate. Two protonated nitrogen atoms in the cation act as donors to the ionized central carboxylate of the anion. These hydrogen bonds form a ring with the graph set symbol R2,2(8). The powder pattern has been submitted to ICDD® for inclusion in the Powder Diffraction File™ (PDF®).
Crystal structure of tamsulosin hydrochloride, C20H29N2O5SCl
Authors: Patel Nilan V. , Golab Joseph T. , Kaduk James A. , Gindhart Amy M. , Blanton Thomas N.
Published: February 2021

The crystal structure of tamsulosin hydrochloride has been solved and refined using synchrotron X-ray powder diffraction data and optimized using density functional techniques. Tamsulosin hydrochloride crystallizes in space groupP21(#4) witha= 7.62988(2),b= 9.27652(2),c= 31.84996(12) Å,β= 93.2221(2)°,V= 2250.734(7) Å3, andZ= 4. In the crystal structure, two arene rings are connected by a carbon chain oriented roughly parallel to thec-axis. The crystal structure is characterized by two slabs of tamsulosin hydrochloride molecules perpendicular to thec-axis. As expected, each of the hydrogens on the protonated nitrogen atoms makes a strong hydrogen bond to one of the chloride anions. The result is to link the cations and anions into columns along theb-axis. One hydrogen atom of each sulfonamide group also makes a hydrogen bond to a chloride anion. The other hydrogen atom of each sulfonamide group forms bifurcated hydrogen bonds to two ether oxygen atoms. The powder pattern is included in the Powder Diffraction File™ as entry 00-065-1415.
Low-molecular-weight heparin administered by subcutaneous catheter is a safe and effective anti-coagulation regimen in selected inpatient infants and children with complex congenital heart disease
Authors: Pardun Nadja , Lemmer Julia , Belker Kristina , Pringsheim Milka , Ewert Peter , Wolf Cordula M.
Published: February 2021

Background/hypothesis:

Disadvantages of intravenous therapeutic unfractionated heparin, the first-line anti-coagulant agent in children with complex congenital heart disease, include unpredictable pharmacokinetics requiring frequent phlebotomies and the need for continuous intravenous access.

Objective:

To compare efficacy and safety of low-molecular-weight heparin administered by a subcutaneous indwelling catheter with intravenous unfractionated heparin.

Materials and methods:

Clinical data from 31 inpatients prospectively enrolled to receive subcutaneous low-molecular-weight heparin were compared with those from a historical group of 44 inpatients receiving intravenous unfractionated heparin. Investigation of parents’ satisfaction by telephone survey.

Results:

The percentage of anti-factor Xa levels outside therapeutic range was lower in the subcutaneous low-molecular-weight heparin group compared with the percentage of activated partial thromboplastin times outside therapeutic range in the intravenous unfractionated heparin group (40% versus 90%, p < 0.001). Neither group had a major complication. Transient local reactions occurred in 19% of patients of the subcutaneous low-molecular-weight heparin group. The number of needle punctures and that of placement of indwelling catheters were significantly lower in the subcutaneous low-molecular-weight heparin compared with the intravenous unfractionated heparin group (p < 0.001). In total, 84.2% of parents in the subcutaneous low-molecular-weight heparin group reported a positive experience when asked about comparison with prior intravenous unfractionated heparin treatment.

Conclusion:

Subcutaneous low-molecular-weight heparin offers a safe anti-coagulation regimen for children with complex congenital heart disease providing more efficient therapeutic anti-coagulation and a reduction in needle punctures, thus causing less pain and anxiety in this children.
Effect of breakfast cereal type on portion size and nutritional implications
Authors: Lewis Isabelle M , Boote Lucy , Butler Tom
Published: February 2021

Objective:

The present study aimed to assess the effect of different types of breakfast cereal (BC) on portion size and the nutritional implications of potential under or overserving.

Design:

A cross-sectional analysis was performed using one BC from the seven established BC manufacturing methods (flaking (F), gun puffed (GP), oven puffed (OP), extruded gun puffed (EGP), shredded wholegrain (SW), biscuit formed (BF) and granola). Participants were asked to pour cereal as if they were serving themselves (freepour). Difference between the freepour and recommended serving size (RSS) was calculated (DFR). The Friedman test followed by Dunn’s multiple comparison test was used to test for a significant differences between cereal categories.

Setting:

City of Chester, North West of the UK.

Participants:

Adults (n 169; n 110 female, 32 (sd 18) years).

Results:

Freepour values were greater than RSS for all categories of BC. Median values for denser cereals such as SW, granola and oats were significantly (P < 0·001) greater than all other categories with granola having the highest median freepour value of 95 g. Median (and range of) DFR weight values for granola were significantly higher than other BC (50·0 g (−24·0 to 267·0 g), P < 0·001). BC with the lowest median DFR were F1 (7·0 g (−20 to 63·0 g)), GP (6·0 g (−26·0 to 69·0 g)), EGP (6·0 g (−26·0 to 56·0 g)), OP (5·0 g (−27·0 to 53·0 g)) and BF (0·0 g (−28·2 to 56·4 g)).

Conclusions:

The degree of overserving may be related to the type of BC with denser cereals more readily overserved. Encouraging manufacturers to reformulate cereals and improving their nutritional properties may have benefit in reducing excess energy intake.
What Stymies Action on Climate Change? Religious Institutions, Marginalization, and Efficacy in Kenya
Authors: Honig Lauren , Smith Amy Erica , Bleck Jaimie
Published: February 2021

Addressing climate change requires coordinated policy responses that incorporate the needs of the most impacted populations. Yet even communities that are greatly concerned about climate change may remain on the sidelines. We examine what stymies some citizens’ mobilization in Kenya, a country with a long history of environmental activism and high vulnerability to climate change. We foreground efficacy—a belief that one’s actions can create change—as a critical link transforming concern into action. However, that link is often missing for marginalized ethnic, socioeconomic, and religious groups. Analyzing interviews, focus groups, and survey data, we find that Muslims express much lower efficacy to address climate change than other religious groups; the gap cannot be explained by differences in science beliefs, issue concern, ethnicity, or demographics. Instead, we attribute it to understandings of marginalization vis-à-vis the Kenyan state—understandings socialized within the local institutions of Muslim communities affected by state repression.
Pakistani Immigrants' Nuanced Beliefs About Shame and Its Regulation
Authors: Collardeau Fanie , Bin Aftab Muhammad Usama , Jibeen Tahira , Woodin Erica
Published: February 2021

Abstract. The present study explored beliefs about shame and coping strategies of Pakistani immigrants to Canada, without imposing Western definitions or theories. Semistructured interviews were conducted with 18 adult Pakistani immigrants to Canada who immigrated within the last 8 years. Grounded theory was used to uncover and illuminate how shame could act as a signal for wrongdoing or emerge as a result of social control and social hierarchies, while in both instances being shaped by and informing complex relational and social contexts. Participants accessed a wide range of positive and negative coping behaviors and prioritized positive coping strategies which included close others and focused on self-improvement. The findings highlight the need for researchers to expand current definitions of shame to render them more inclusive of non-Western worldviews and to honor the diversity in metacognitions or beliefs about shame present in different cultural groups. Future research may also benefit from exploring how shame may be felt as a response to power differentials, and how this may impact individuals' experiences of immigration. It is important for practitioners working with Pakistani immigrants to Canada to honor clients' nuanced and complex cultural and religious knowledge about shame, as Pakistani immigrants' beliefs about shame and their proactive stance toward the regulation of this emotion are likely to be protective. We also encourage therapists to be open to discussing sources of shame (e.g., personal vs. imposed by others) and systemic, structural inequalities which may be important in explaining individuals' emotional experience.
Antarctic Circumpolar Current Impacts on Internal Wave Life Cycles
Authors: Waterman S. , Meyer A. , Polzin K. L. , Naveira Garabato A. C. , Sheen K. L.
Published: February 2021

Major gaps exist in our understanding of the pathways between internal wave generation and breaking in the Southern Ocean, with important implications for the distribution of internal wave‐driven mixing, the sensitivity of ocean mixing rates and patterns to changes in the ocean environment, and the necessary ingredients of mixing parameterizations. Here we assess the dominant processes in internal wave evolution by characterizing wave and mesoscale flow scales based on full‐depth in situ measurements in a Southern Ocean mixing hot spot and a ray tracing calculation. The exercise highlights the importance of Antarctic Circumpolar Current jets as a dominant influence on internal wave life cycles through advection, the modification of wave characteristics via wave‐mean flow interactions, and the set‐up of critical layers for both upward‐ and downward‐propagating waves. Our findings suggest that it is important to represent mesoscale flow impacts in parameterizations of internal wave‐driven mixing in the Southern Ocean.
A Physics‐Based Universal Indicator for Vertical Decoupling and Mixing Across Canopies Architectures and Dynamic Stabilities
Authors: Peltola O. , Lapo K. , Thomas C. K.
Published: February 2021

Air flows may be decoupled from the underlying surface either due to strong stratification of air or due to canopy drag suppressing cross‐canopy mixing. During decoupling, turbulent fluxes vary with height and hence identification of decoupled periods is crucial for the estimation of surface fluxes with the eddy covariance (EC) technique and computation of ecosystem‐scale carbon, heat, and water budgets. A new indicator for identifying the decoupled periods is derived using forces (buoyancy and canopy drag) hindering movement of a downward propagating air parcel. This approach improves over the existing methods since (1) changes in forces hindering the coupling are accounted for, and (2) it is based on first principles and not on ad hoc empirical correlations. The applicability of the method is demonstrated at two contrasting EC sites (flat open terrain, boreal forest) and should be applicable also at other EC sites above diverse ecosystems (from grasslands to dense forests).
Tropical Cyclone Frequency Under Varying SSTs in Aquaplanet Simulations
Authors: Burnett Adam C. , Sheshadri Aditi , Silvers Levi G. , Robinson Thomas
Published: February 2021

Global tropical cyclone (TC) frequency is investigated in a 50‐km‐resolution aquaplanet model forced by zonally symmetric sea surface temperature (SST). TC frequency per unit area is found to be proportional to the Coriolis parameter at the intertropical convergence zone (ITCZ), as defined by the latitude of maximum precipitation. As the latitude of maximum SST is shifted northward from the equator, the precipitation maximum moves northward and TC frequency increases. When the SST maximum is shifted northward past 25°N, the precipitation maximum remains between 15°N and 20°N, and TC frequency per unit area is approximately constant. When applied to observed precipitation and SST data, the same scaling captures a substantial fraction of observed TCs. Results suggest that future changes in TC activity will be modulated by changes in the large‐scale circulation, and in particular that the ITCZ location is an important determinant of the number of TCs.
Parameterizing the Impact of Seawater Temperature and Irradiance on Dimethylsulfide (DMS) in the Great Barrier Reef and the Contribution of Coral Reefs to the Global Sulfur Cycle
Authors: Jackson R. L. , Gabric A. J. , Matrai P. A. , Woodhouse M. T. , Cropp R. , Jones G. B. , Deschaseaux E. S. M. , Omori Y. , McParland E. L. , Swan H. B. , Tanimoto H.
Published: February 2021

Biogenic emissions of dimethylsulfide (DMS) are an important source of sulfur to the atmosphere, with implications for aerosol formation and cloud albedo over the ocean. Natural aerosol sources constitute the largest uncertainty in estimates of aerosol radiative forcing and climate and thus, an improved understanding of DMS sources is needed. Coral reefs are strong point sources of DMS; however, this coral source of biogenic sulfur is not explicitly included in climatologies or in model simulations. Consequently, the role of coral reefs in local and regional climate remains uncertain. We aim to improve the representation of tropical coral reefs in DMS databases by calculating a climatology of seawater DMS concentration (DMSw) and sea‐air flux in the Great Barrier Reef (GBR), Australia. DMSwis calculated from remotely sensed observations of sea surface temperature and photosynthetically active radiation using a multiple linear regression model derived from field observations of DMSwin the GBR. We estimate that coral reefs and lagoon waters in the GBR (∼347,000 km2) release 0.03–0.05 Tg yr−1of DMS (0.02 Tg yr−1of sulfur). Based on this estimate, global tropical coral reefs (∼600,000 km2) could emit 0.08 Tg yr−1of DMS (0.04 Tg yr−1of sulfur), with the potential to influence the local radiative balance.
Improved Circulation in the Northern Hemisphere by Adjusting Gravity Wave Drag Parameterizations in Seasonal Experiments With ICON‐NWP
Authors: Köhler Raphael , Handorf Dörthe , Jaiser Ralf , Dethloff Klaus , Zängl Günther , Majewski Detlev , Rex Markus
Published: February 2021

The stratosphere is one of the main potential sources for subseasonal to seasonal predictability in midlatitudes in winter. The ability of an atmospheric model to realistically simulate the stratospheric dynamics is essential in order to move forward in the field of seasonal predictions in midlatitudes. Earlier studies with the ICOsahedral Nonhydrostatic atmospheric model (ICON) point out that stratospheric westerlies in ICON are underestimated. This is the first extensive study on the evaluation of Northern Hemisphere stratospheric winter circulation with ICON in numerical weather prediction (NWP) mode. Seasonal experiments with the default setup are able to reproduce the basic climatology of the stratospheric polar vortex. However, westerlies are too weak and major stratospheric warmings too frequent in ICON. Both a reduction of the nonorographic, and a reduction of the orographic gravity wave and wake drag lead to a strengthening of the stratospheric vortex and a bias reduction, in particular in January. However, the effect of the nonorographic gravity wave drag scheme on the stratosphere is stronger. Stratosphere‐troposphere coupling is intensified and more realistic due to a reduced gravity wave drag. Furthermore, an adjustment of the subgrid‐scale orographic drag parameterization leads to a significant error reduction in the mean sea level pressure. As a result of these findings, we present our current suggested improved setup for seasonal experiments with ICON‐NWP.
Sooty Layers in Stalagmites Record Human Activity in Caves
Authors: Kornei Katherine
Published: February 2021

Scientists analyzing cave formations in Turkey find layers of soot and charcoal in stalagmites, revealing that humans—and their fires—occupied caves thousands of years ago.
Evidence of Small Scale Plasma Irregularity Effects on Whistler Mode Chorus Propagation
Authors: Hosseini Poorya , Agapitov Oleksiy , Harid Vijay , Gołkowski Mark
Published: February 2021

The impact of randomly distributed field‐aligned density irregularities on whistler‐mode wave propagation is investigated using full‐wave simulations and multipoint spacecraft observations. The irregularities are modeled as randomized density perturbations between 1% and 10% of the nominal background density value with scales of ∼10–60 km transverse and ∼50–500 km along the background magnetic field. The density irregularities affect whistler wave propagation and lead to spatial modulation of wave average power density accompanied by spreading of the wave normal angle distribution. Wave power variation is shown to statistically increase with the depth of density irregularities. The simulation results are in good agreement with the observed correlations of chorus power and variation of the plasma density from multipoint observations by the four Magnetosphere MultiScale spacecraft. The change in fundamental wave properties from scattering from these irregularities affects the efficiency of wave‐particle interactions in the radiation belts and needs to be incorporated into large‐scale energetic‐particle flux models.
Targeting cancer stem cells for reversing therapy resistance: mechanism, signaling, and prospective agents
Authors: Zhou He-Ming , Zhang Ji-Gang , Zhang Xue , Li Qin
Published: February 2021

Cancer stem cells (CSCs) show a self-renewal capacity and differentiation potential that contribute to tumor progression and therapy resistance. However, the underlying processes are still unclear. Elucidation of the key hallmarks and resistance mechanisms of CSCs may help improve patient outcomes and reduce relapse by altering therapeutic regimens. Here, we reviewed the identification of CSCs, the intrinsic and extrinsic mechanisms of therapy resistance in CSCs, the signaling pathways of CSCs that mediate treatment failure, and potential CSC-targeting agents in various tumors from the clinical perspective. Targeting the mechanisms and pathways described here might contribute to further drug discovery and therapy.
Nonnutritive sweeteners can promote the dissemination of antibiotic resistance through conjugative gene transfer
Authors: Yu Zhigang , Wang Yue , Lu Ji , Bond Philip L , Guo Jianhua
Published: February 2021

Antimicrobial resistance (AMR) poses a worldwide threat to human health and biosecurity. The spread of antibiotic resistance genes (ARGs) via conjugative plasmid transfer is a major contributor to the evolution of this resistance. Although permitted as safe food additives, compounds such as saccharine, sucralose, aspartame, and acesulfame potassium that are commonly used as nonnutritive sweeteners have recently been associated with shifts in the gut microbiota similar to those caused by antibiotics. As antibiotics can promote the spread of antibiotic resistance genes (ARGs), we hypothesize that these nonnutritive sweeteners could have a similar effect. Here, we demonstrate for the first time that saccharine, sucralose, aspartame, and acesulfame potassium could promote plasmid-mediated conjugative transfer in three established conjugation models between the same and different phylogenetic strains. The real-time dynamic conjugation process was visualized at the single-cell level. Bacteria exposed to the tested compounds exhibited increased reactive oxygen species (ROS) production, the SOS response, and gene transfer. In addition, cell membrane permeability increased in both parental bacteria under exposure to the tested compounds. The expression of genes involved in ROS detoxification, the SOS response, and cell membrane permeability was significantly upregulated under sweetener treatment. In conclusion, exposure to nonnutritive sweeteners enhances conjugation in bacteria. Our findings provide insight into AMR spread and indicate the potential risk associated with the presence of nonnutritive sweeteners.
HERVs establish a distinct molecular subtype in stage II/III colorectal cancer with poor outcome
Authors: Golkaram Mahdi , Salmans Michael L. , Kaplan Shannon , Vijayaraghavan Raakhee , Martins Marta , Khan Nafeesa , Garbutt Cassandra , Wise Aaron , Yao Joyee , Casimiro Sandra , Abreu Catarina , Macedo Daniela , Costa Ana Lúcia , Alvim Cecília , Mansinho André , Filipe Pedro , Marques da Costa Pedro , Fernandes Afonso , Borralho Paula , Ferreira Cristina , Aldeia Fernando , Malaquias João , Godsey Jim , So Alex , Pawlowski Traci , Costa Luis , Zhang Shile , Liu Li
Published: February 2021

Colorectal cancer (CRC) is one of the most lethal malignancies. The extreme heterogeneity in survival rate is driving the need for new prognostic biomarkers. Human endogenous retroviruses (hERVs) have been suggested to influence tumor progression, oncogenesis and elicit an immune response. We examined multiple next-generation sequencing (NGS)-derived biomarkers in 114 CRC patients with paired whole-exome and whole-transcriptome sequencing (WES and WTS, respectively). First, we demonstrate that the median expression of hERVs can serve as a potential biomarker for prognosis, relapse, and resistance to chemotherapy in stage II and III CRC. We show that hERV expression and CD8+ tumor-infiltrating T-lymphocytes (TILs) synergistically stratify overall and relapse-free survival (OS and RFS): the median OS of the CD8-/hERV+ subgroup was 29.8 months compared with 37.5 months for other subgroups (HR = 4.4, log-rank P < 0.001). Combing NGS-based biomarkers (hERV/CD8 status) with clinicopathological factors provided a better prediction of patient survival compared to clinicopathological factors alone. Moreover, we explored the association between genomic and transcriptomic features of tumors with high hERV expression and establish this subtype as distinct from previously described consensus molecular subtypes of CRC. Overall, our results underscore a previously unknown role for hERVs in leading to a more aggressive subtype of CRC.
Miura-ori enabled stretchable circuit boards
Authors: Li Yongkai , Liu Weixuan , Deng Yang , Hong Wei , Yu Hongyu
Published: February 2021

Origami, an ancient form of papercraft, provides a way to develop functional structures for engineering applications. In this paper, we report an approach to design and manufacture a stretchable circuit board (SCB) with origami structures. The benefits of developable, flat-foldable, and rigid-foldable origami-based structures as SCBs are discussed, and a representative structure, Miura fold (or Miura-ori), is chosen to be investigated. Under the constraints induced by the mounted components’ dimensions, the Miura-ori structures for specific applications can be defined. We propose three methods for better fabrication, including direct folding, stiffness modification, and kirigami enhancement, to improve a planar sheet’s foldability. A wearable ECG (electrocardiogram) system based on MO-SCB (Miura-ori enabled SCB) technology is built, and the stretchable portion is made of commercial FPCBs (flexible printed circuit board), providing desired stretchability and reliability. The proposed technology routine is compatible with industrial production and may pave the application of stretchable electronics.
Timing variability and midfrontal ~4 Hz rhythms correlate with cognition in Parkinson’s disease
Authors: Singh Arun , Cole Rachel C. , Espinoza Arturo I. , Evans Aron , Cao Scarlett , Cavanagh James F. , Narayanan Nandakumar S.
Published: February 2021

Patients with Parkinson’s disease (PD) can have significant cognitive dysfunction; however, the mechanisms for these cognitive symptoms are unknown. Here, we used scalp electroencephalography (EEG) to investigate the cortical basis for PD-related cognitive impairments during interval timing, which requires participants to estimate temporal intervals of several seconds. Time estimation is an ideal task demand for investigating cognition in PD because it is simple, requires medial frontal cortical areas, and recruits basic executive processes such as working memory and attention. However, interval timing has never been systematically studied in PD patients with cognitive impairments. We report three main findings. First, 71 PD patients had increased temporal variability compared to 37 demographically matched controls, and this variability correlated with cognitive dysfunction as measured by the Montreal Cognitive Assessment (MOCA). Second, PD patients had attenuated ~4 Hz EEG oscillatory activity at midfrontal electrodes in response to the interval-onset cue, which was also predictive of MOCA. Finally, trial-by-trial linear mixed-effects modeling demonstrated that cue-triggered ~4 Hz power predicted subsequent temporal estimates as a function of PD and MOCA. Our data suggest that impaired cue-evoked midfrontal ~4 Hz activity predicts increased timing variability that is indicative of cognitive dysfunction in PD. These findings link PD-related cognitive dysfunction with cortical mechanisms of cognitive control, which could advance novel biomarkers and neuromodulation for PD.
A quantum algorithm for string matching
Authors: Niroula Pradeep , Nam Yunseong
Published: February 2021

Algorithms that search for a pattern within a larger data-set appear ubiquitously in text and image processing. Here, we present an explicit, circuit-level implementation of a quantum pattern-matching algorithm that matches a search string (pattern) of length M inside a longer text of length N. Our algorithm has a time complexity of $$\tilde{O}(\sqrt{N})$$

O

̃

(

N

)

, while the space complexity remains modest at O(N + M). We report the quantum gate counts relevant for both pre-fault-tolerant and fault-tolerant regimes.
Tropical cyclone simulations over Bangladesh at convection permitting 4.4 km & 1.5 km resolution
Authors: Steptoe Hamish , Savage Nicholas Henry , Sadri Saeed , Salmon Kate , Maalick Zubair , Webster Stuart
Published: February 2021

High resolution simulations at 4.4 km and 1.5 km resolution have been performed for 12 historical tropical cyclones impacting Bangladesh. We use the European Centre for Medium-Range Weather Forecasting 5thgeneration Re-Analysis (ERA5) to provide a 9-member ensemble of initial and boundary conditions for the regional configuration of the Met Office Unified Model. The simulations are compared to the original ERA5 data and the International Best Track Archive for Climate Stewardship (IBTrACS) tropical cyclone database for wind speed, gust speed and mean sea-level pressure. The 4.4 km simulations show a typical increase in peak gust speed of 41 to 118 knots relative to ERA5, and a deepening of minimum mean sea-level pressure of up to −27 hPa, relative to ERA5 and IBTrACS data. The downscaled simulations compare more favourably with IBTrACS data than the ERA5 data suggesting tropical cyclone hazards in the ERA5 deterministic output may be underestimated. The dataset is freely available fromhttps://doi.org/10.5281/zenodo.3600201.
Social connectedness and negative affect uniquely explain individual differences in response to emotional ambiguity
Authors: Neta Maital , Brock Rebecca L.
Published: February 2021

Negativity bias is not only central to mood and anxiety disorders, but can powerfully impact our decision-making across domains (e.g., financial, medical, social). This project builds on previous work examining negativity bias using dual-valence ambiguity. Specifically, although some facial expressions have a relatively clear negative (angry) or positive valence (happy), surprised expressions are interpreted negatively by some and positively by others, providing insight into one’s valence bias. Here, we examine putative sources of variability that distinguish individuals with a more negative versus positive valence bias using structural equation modeling. Our model reveals that one’s propensity toward negativity (operationalized as temperamental negative affect and internalizing symptomology) predicts valence bias particularly in older adulthood when a more positive bias is generally expected. Further, variability in social connectedness (a propensity to seek out social connections, use those connections to regulate one’s own emotions, and be empathic) emerges as a notable and unique predictor of valence bias, likely because these traits help to override an initial, default negativity. We argue that this task represents an important approach to examining variability in affective bias, and can be specifically useful across the lifespan and in populations with internalizing disorders or even subclinical symptomology.
T cell-tropic HIV efficiently infects alveolar macrophages through contact with infected CD4+ T cells
Authors: Schiff Abigail E. , Linder Alice H. , Luhembo Shillah N. , Banning Stephanie , Deymier Martin J. , Diefenbach Thomas J. , Dickey Amy K. , Tsibris Athe M. , Balazs Alejandro B. , Cho Josalyn L. , Medoff Benjamin D. , Walzl Gerhard , Wilkinson Robert J. , Burgers Wendy A. , Corleis Björn , Kwon Douglas S.
Published: February 2021

Alveolar macrophages (AMs) are critical for defense against airborne pathogens and AM dysfunction is thought to contribute to the increased burden of pulmonary infections observed in individuals living with HIV-1 (HIV). While HIV nucleic acids have been detected in AMs early in infection, circulating HIV during acute and chronic infection is usually CCR5 T cell-tropic (T-tropic) and enters macrophages inefficiently in vitro. The mechanism by which T-tropic viruses infect AMs remains unknown. We collected AMs by bronchoscopy performed in HIV-infected, antiretroviral therapy (ART)-naive and uninfected subjects. We found that viral constructs made with primary HIV envelope sequences isolated from both AMs and plasma were T-tropic and inefficiently infected macrophages. However, these isolates productively infected macrophages when co-cultured with HIV-infected CD4+ T cells. In addition, we provide evidence that T-tropic HIV is transmitted from infected CD4+ T cells to the AM cytosol. We conclude that AM-derived HIV isolates are T-tropic and can enter macrophages through contact with an infected CD4+ T cell, which results in productive infection of AMs. CD4+ T cell-dependent entry of HIV into AMs helps explain the presence of HIV in AMs despite inefficient cell-free infection, and may contribute to AM dysfunction in people living with HIV.
Multispecies for multifunctions: combining four complementary species enhances multifunctionality of sown grassland
Authors: Suter Matthias , Huguenin-Elie Olivier , Lüscher Andreas
Published: February 2021

Assessing the overall performance of ecosystems requires a quantitative evaluation of multifunctionality. We investigated plant species diversity effects on individual functions and overall multifunctionality in a grassland experiment with sown monocultures and mixtures comprising four key grass and legume species. Nitrogen fertilisation rates were 50, 150, and 450 kg N ha−1 yr−1 (N50, N150, N450). Ten functions were measured representing forage production, N cycling, and forage quality, all being related to either productivity or environmental footprint. Multifunctionality was analysed by a novel approach using the mean log response ratio across functions. Over three experimental years, mixture effects benefited all forage production and N cycling functions, while sustaining high forage quality. Thus, mixture effects did not provoke any trade-off among the analysed functions. High N fertilisation rates generally diminished mixture benefits. Multifunctionality of four-species mixtures was considerably enhanced, and mixture overall performance was up to 1.9 (N50), 1.8 (N150), and 1.6 times (N450) higher than in averaged monocultures. Multifunctionality of four-species mixtures at N50 was at least as high as in grass monocultures at N450. Sown grass–legume mixtures combining few complementary species at low to moderate N fertilisation sustain high multifunctionality and are a ‘ready-to-use’ option for the sustainable intensification of agriculture.
Temporal and cultural limits of privacy in smartphone app usage
Authors: Sekara Vedran , Alessandretti Laura , Mones Enys , Jonsson Håkan
Published: February 2021

Large-scale collection of human behavioural data by companies raises serious privacy concerns. We show that behaviour captured in the form of application usage data collected from smartphones is highly unique even in large datasets encompassing millions of individuals. This makes behaviour-based re-identification of users across datasets possible. We study 12 months of data from 3.5 million people from 33 countries and show that although four apps are enough to uniquely re-identify 91.2% of individuals using a simple strategy based on public information, there are considerable seasonal and cultural variations in re-identification rates. We find that people have more unique app-fingerprints during summer months making it easier to re-identify them. Further, we find significant variations in uniqueness across countries, and reveal that American users are the easiest to re-identify, while Finns have the least unique app-fingerprints. We show that differences across countries can largely be explained by two characteristics of the country specific app-ecosystems: the popularity distribution and the size of app-fingerprints. Our work highlights problems with current policies intended to protect user privacy and emphasizes that policies cannot directly be ported between countries. We anticipate this will nuance the discussion around re-identifiability in digital datasets and improve digital privacy.
Breakup of a long-period comet as the origin of the dinosaur extinction
Authors: Siraj Amir , Loeb Abraham
Published: February 2021

The origin of the Chicxulub impactor, which is attributed as the cause of the K/T mass extinction event, is an unsolved puzzle. The background impact rates of main-belt asteroids and long-period comets have been previously dismissed as being too low to explain the Chicxulub impact event. Here, we show that a fraction of long-period comets are tidally disrupted after passing close to the Sun, each producing a collection of smaller fragments that cross the orbit of Earth. This population could increase the impact rate of long-period comets capable of producing Chicxulub impact events by an order of magnitude. This new rate would be consistent with the age of the Chicxulub impact crater, thereby providing a satisfactory explanation for the origin of the impactor. Our hypothesis explains the composition of the largest confirmed impact crater in Earth’s history as well as the largest one within the last million years. It predicts a larger proportion of impactors with carbonaceous chondritic compositions than would be expected from meteorite falls of main-belt asteroids.
Exercise alters the mitochondrial proteostasis and induces the mitonuclear imbalance and UPRmt in the hypothalamus of mice
Authors: Braga Renata R. , Crisol Barbara M. , Brícola Rafael S. , Sant’ana Marcella R. , Nakandakari Susana C. B. R. , Costa Suleyma O. , Prada Patrícia O. , da Silva Adelino S. R. , Moura Leandro P. , Pauli José R. , Cintra Dennys E. , Ropelle Eduardo R.
Published: February 2021

The maintenance of mitochondrial activity in hypothalamic neurons is determinant to the control of energy homeostasis in mammals. Disturbs in the mitochondrial proteostasis can trigger the mitonuclear imbalance and mitochondrial unfolded protein response (UPRmt) to guarantee the mitochondrial integrity and function. However, the role of mitonuclear imbalance and UPRmt in hypothalamic cells are unclear. Combining the transcriptomic analyses from BXD mice database and in vivo experiments, we demonstrated that physical training alters the mitochondrial proteostasis in the hypothalamus of C57BL/6J mice. This physical training elicited the mitonuclear protein imbalance, increasing the mtCO-1/Atp5a ratio, which was accompanied by high levels of UPRmt markers in the hypothalamus. Also, physical training increased the maximum mitochondrial respiratory capacity in the brain. Interestingly, the transcriptomic analysis across several strains of the isogenic BXD mice revealed that hypothalamic mitochondrial DNA-encoded genes were negatively correlated with body weight and several genes related to the orexigenic response. As expected, physical training reduced body weight and food intake. Interestingly, we found an abundance of mt-CO1, a mitochondrial DNA-encoded protein, in NPY-producing neurons in the lateral hypothalamus nucleus of exercised mice. Collectively, our data demonstrated that physical training altered the mitochondrial proteostasis and induced the mitonuclear protein imbalance and UPRmt in hypothalamic cells.
Lag synchronization of coupled time-delayed FitzHugh–Nagumo neural networks via feedback control
Authors: Ibrahim Malik Muhammad , Kamran Muhammad Ahmad , Mannan Malik Muhammad Naeem , Jung Il Hyo , Kim Sangil
Published: February 2021

Synchronization plays a significant role in information transfer and decision-making by neurons and brain neural networks. The development of control strategies for synchronizing a network of chaotic neurons with time delays, different direction-dependent coupling (unidirectional and bidirectional), and noise, particularly under external disturbances, is an essential and very challenging task. Researchers have extensively studied the synchronization mechanism of two coupled time-delayed neurons with bidirectional coupling and without incorporating the effect of noise, but not for time-delayed neural networks. To overcome these limitations, this study investigates the synchronization problem in a network of coupled FitzHugh–Nagumo (FHN) neurons by incorporating time delays, different direction-dependent coupling (unidirectional and bidirectional), noise, and ionic and external disturbances in the mathematical models. More specifically, this study investigates the synchronization of time-delayed unidirectional and bidirectional ring-structured FHN neuronal systems with and without external noise. Different gap junctions and delay parameters are used to incorporate time-delay dynamics in both neuronal networks. We also investigate the influence of the time delays between connected neurons on synchronization conditions. Further, to ensure the synchronization of the time-delayed FHN neuronal networks, different adaptive control laws are proposed for both unidirectional and bidirectional neuronal networks. In addition, necessary and sufficient conditions to achieve synchronization are provided by employing the Lyapunov stability theory. The results of numerical simulations conducted for different-sized multiple networks of time-delayed FHN neurons verify the effectiveness of the proposed adaptive control schemes.
CRISPR/Cas9 mediated mutagenesis of MORE AXILLARY GROWTH 1 in tomato confers resistance to root parasitic weed Phelipanche aegyptiaca
Authors: Bari Vinay Kumar , Nassar Jackline Abu , Aly Radi
Published: February 2021

Root parasitic weeds infect numerous economically important crops, affecting total yield quantity and quality. A lack of an efficient control method limits our ability to manage newly developing and more virulent races of root parasitic weeds. To control the parasite induced damage in most host crops, an innovative biotechnological approach is urgently required. Strigolactones (SLs) are plant hormones derived from carotenoids via a pathway involving the Carotenoid Cleavage Dioxygenase (CCD) 7, CCD8 and More Axillary Growth 1 (MAX1) genes. SLs act as branching inhibitory hormones and strictly required for the germination of root parasitic weeds. Here, we demonstrate that CRISPR/Cas9-mediated targted editing of SL biosynthetic gene MAX1, in tomato confers resistance against root parasitic weed Phelipanche aegyptiaca. We designed sgRNA to target the third exon of MAX1 in tomato plants using the CRISPR/Cas9 system. The T0 plants were edited very efficiently at the MAX1 target site without any non-specific off-target effects. Genotype analysis of T1 plants revealed that the introduced mutations were stably passed on to the next generation. Notably, MAX1-Cas9 heterozygous and homozygous T1 plants had similar morphological changes that include excessive growth of axillary bud, reduced plant height and adventitious root formation relative to wild type. Our results demonstrated that, MAX1-Cas9 mutant lines exhibit resistance against root parasitic weed P. aegyptiaca due to reduced SL (orobanchol) level. Moreover, the expression of carotenoid biosynthetic pathway gene PDS1 and total carotenoid level was altered, as compared to wild type plants. Taking into consideration, the impact of root parasitic weeds on the agricultural economy and the obstacle to prevent and eradicate them, the current study provides new aspects into the development of an efficient control method that could be used to avoid germination of root parasitic weeds.
Palladin isoforms 3 and 4 regulate cancer-associated fibroblast pro-tumor functions in pancreatic ductal adenocarcinoma
Authors: Alexander J. I. , Vendramini-Costa D. B. , Francescone R. , Luong T. , Franco-Barraza J. , Shah N. , Gardiner J. C. , Nicolas E. , Raghavan K. S. , Cukierman E.
Published: February 2021

Pancreatic Ductal Adenocarcinoma (PDAC) has a five-year survival under 10%. Treatment is compromised due to a fibrotic-like stromal remodeling process, known as desmoplasia, which limits therapeutic perfusion, supports tumor progression, and establishes an immunosuppressive microenvironment. These processes are driven by cancer-associated fibroblasts (CAFs), functionally activated through transforming growth factor beta1 (TGFβ1). CAFs produce a topographically aligned extracellular matrix (ECM) that correlates with reduced overall survival. Paradoxically, ablation of CAF populations results in a more aggressive disease, suggesting CAFs can also restrain PDAC progression. Thus, unraveling the mechanism(s) underlying CAF functions could lead to therapies that reinstate the tumor-suppressive features of the pancreatic stroma. CAF activation involves the f-actin organizing protein palladin. CAFs express two palladin isoforms (iso3 and iso4) which are up-regulated in response to TGFβ1. However, the roles of iso3 and iso4 in CAF functions remain elusive. Using a CAF-derived ECM model, we uncovered that iso3/iso4 are required to sustain TGFβ1-dependent CAF activation, secrete immunosuppressive cytokines, and produce a pro-tumoral ECM. Findings demonstrate a novel role for CAF palladin and suggest that iso3/iso4 regulate both redundant and specific tumor-supportive desmoplastic functions. This study highlights the therapeutic potential of targeting CAFs to restore fibroblastic anti-tumor activity in the pancreatic microenvironment.
Preventable fractions of cancer incidence attributable to 7-years weight gain in the Norwegian Women and Cancer (NOWAC) study
Authors: da Silva Marisa , Laaksonen Maarit A. , Lissner Lauren , Weiderpass Elisabete , Rylander Charlotta
Published: February 2021

There is a lack of tangible measures for directed public health action to halt the increase in weight and cancer. We estimated the fraction and preventable cases of all and major body fatness-related cancers attributable to 7-years weight gain (≥ 2 kg). We assessed validated self-reported anthropometrics from 44,114 women aged 34–49 years at the enrolment in 1991–1992 and from a second questionnaire in 1998, with follow-up through December 31, 2015. Over 18 years, 3216 body fatness-related cancers and 2041 deaths were reported. Nearly 70% of women experienced weight gain and the average weight change was 4 kg. We observed a substantial proportional impact of weight gain on pancreatic cancer with a population attributable fraction (PAF) of 41.8% (95% CI 8.1–63.1) and a high absolute impact on postmenopausal breast cancer with 4403 preventable cases (95% CI 1064–7299) and a PAF of 16.8% (95% CI 4.1–27.8), and colorectal cancer with 3857 preventable cases (95% CI 1313–5990) and a PAF of 22.6% (95% CI 7.7–35.1). Avoiding weight gain over seven years in middle adulthood could have prevented a considerable proportion of the cancer burden and thousands of cancer cases in women in Norway.
Entropy generation and dissipative heat transfer analysis of mixed convective hydromagnetic flow of a Casson nanofluid with thermal radiation and Hall current
Authors: Sahoo A. , Nandkeolyar R.
Published: February 2021

The present article provides a detailed analysis of entropy generation on the unsteady three-dimensional incompressible and electrically conducting magnetohydrodynamic flow of a Casson nanofluid under the influence of mixed convection, radiation, viscous dissipation, Brownian motion, Ohmic heating, thermophoresis and heat generation. At first, similarity transformation is used to transform the governing nonlinear coupled partial differential equations into nonlinear coupled ordinary differential equations, and then the resulting highly nonlinear coupled ordinary differential equations are numerically solved by the utilization of spectral quasi-linearization method. Moreover, the effects of pertinent flow parameters on velocity distribution, temperature distribution, concentration distribution, entropy generation and Bejan number are depicted prominently through various graphs and tables. It can be analyzed from the graphs that the Casson parameter acts as an assisting parameter towards the temperature distribution in the absence of viscous and Joule dissipations, while it has an adverse effect on temperature under the impacts of viscous and Joule dissipations. On the contrary, entropy generation increases significantly for larger Brinkman number, diffusive variable and concentration ratio parameter, whereas the reverse effects of these parameters on Bejan number are examined. Apart from this, the numerical values of some physical quantities such as skin friction coefficients in x and z directions, local Nusselt number and Sherwood number for the variation of the values of pertinent parameters are displayed in tabular forms. A quadratic multiple regression analysis for these physical quantities has also been carried out to improve the present model’s effectiveness in various industrial and engineering areas. Furthermore, an appropriate agreement is obtained on comparing the present results with previously published results.