Miracle-dz/UniFAR-FTUs huggingface dataset:
Invasion of hepatocytes by Plasmodium sporozoites requires cGMP‐dependent protein kinase and calcium dependent protein kinase 4

Invasion of hepatocytes by sporozoites is essential for Plasmodium to initiate infection of the mammalian host. The parasite's subsequent intracellular differentiation in the liver is the first developmental step of its mammalian cycle. Despite their biological significance, surprisingly little is known of the signalling pathways required for sporozoite invasion. We report that sporozoite invasion of hepatocytes requires signalling through two second‐messengers – cGMP mediated by the parasite's cGMP‐dependent protein kinase (PKG), and Ca2+, mediated by the parasite's calcium‐dependent protein kinase 4 (CDPK4). Sporozoites expressing a mutated form of Plasmodium berghei PKG or carrying a deletion of the CDPK4 gene are defective in invasion of hepatocytes. Using specific and potent inhibitors of Plasmodium PKG and CDPK4, we demonstrate that PKG and CDPK4 are required for sporozoite motility, and that PKG regulates the secretion of TRAP, an adhesin that is essential for motility. Chemical inhibition of PKG decreases parasite egress from hepatocytes by inhibiting either the formation or release of merosomes. In contrast, genetic inhibition of CDPK4 does not significantly decrease the number of merosomes. By revealing the requirement for PKG and CDPK4 in Plasmodium sporozoite invasion, our work enables a better understanding of kinase pathways that act in different Plasmodium stages.
Friction measurement indicating the transition between fully flooded and starved regimes in elasto-hydrodynamic lubrication

Lubricant starvation in rolling element bearings can have different origins, such as high speed, large size or grease lubrication. However, the overall result is a performance reduction, involving a friction increase, a bearing life decrease or both. As such it is desirable to be able to predict when starvation will occur for a certain combination of geometry, operating conditions and lubricant. Previous work used optical interferometry to predict the onset of starvation and the ensuing oil film thickness reduction. A starvation parameter was derived linking lubrication parameters (viscosity), amount of oil and operating conditions (load, speed) to predict the onset of starvation. The current paper attempts to predict the onset of starvation through friction measurements on a ball-on-disc test device. The starvation parameter values obtained from friction measurements are similar to the ones found through optical interferometry.
Assessing Collagen Nanoscale Thin Films Heterogeneity by AFM Multimode Imaging and Nanoindetation for NanoBioMedical Applications

Collagen due to its filamentous shape and unique properties is a very promising molecule for the development of nanostructures, scaffolds, cell culture platforms and nanobiomaterials. Furthermore, collagen thin films are of great interest as they can cover non-biological surfaces in medical devices and sensors so as to offer them biocompatibility. Since surface nanotopography and mechanical properties can influence cell-biomaterial interactions it is of crucial im- portance to nano-characterize collagen surface and heterogeneity. Nano-characterization can be performed with Atomic Force Microscopy (AFM), which operates in a variety of modes/techniques and can offer a wide range of information, from topography to mechanical properties. In this paper it was sought to gain insights of structural and mechanical hetero- geneity of collagen fibers in thin films by combining AFM multimode-imaging, including phase imaging, with quantita- tive measurements through nanoindentation. The results demonstrated that the overlap-gap regions on collagen fibers (D-periodicity) yield a significant phase contrast, due to different mechanical properties. In addition, phase contrast was also demonstrated in collagen 'kinks', which provides evidence that collagen fiber shell and core possess different properties. The mechanical heterogeneity of the collagen fibers in the kink areas was confirmed by AFM-nanoindentation and the obtained quantitative measurements. In addition, AFM multimode imaging performance was demonstrated on fibroblasts cultured on collagen thin films. The correlation between the heterogeneous structure and the mechanical properties of collagen fibers in thin films will enable the design and development of biomaterials and tissue scaffolds with improved properties.
Organizational Forgetting/Unlearning: The Dark Side of the Absorptive Capacity

During the past twenty years, absorptive capacity has become one of the constructs most widely used in diverse lines of work on the subject of organisational research. Initially, Cohen & Levinthal (1998,1990) defined absorptive capacity as the ability of a company to recognise the value of knowledge from the environment, assimilate it and exploit it for commercial purposes, with its development being a critical factor in obtaining a competitive advantage. The enormous potential for explanation of the construct (Lane et al., 2002) has led to its use in more than one thousand publications indexed in research lines as organisational learning (Simonin, 1999; Barkema & Vermeulen, 1998), knowledge management (Szulanski, 1996; Ahuja & Katila, 2001), strategic alliances (Lane & Lubatkin, 1998; Lane et al., 2001) and innovation management (Kim & Kogut, 1996; Van den Bosch et al., 1999). The application of the absorptive capacity in different, important, complex organisational phenomena has given rise to the use of diverse measures which are not clearly seen to converge in the same construct (Zahra & George, 2002). This has led some investigators to try and reconceptualise the construct absorptive capacity (Zahra & George, 2002; Lane et al.; 2002; Van den Bosch et al., 2003; Fernandez, 2005; Lane et al., 2006), obtaining similar results which offer a new starting point for conducting research into the construct. These publications propose various lines of research about how to study the construction of a sustainable competitive advantage through possessing absorptive capacity. However, in our opinion, investigating the absorptive capacity of a company is merely a part of this research, for which reason, we postulate that research into the development and maintenance of absorptive capacity is equally important as investigating the causes and circumstances involved in the loss of this capacity. Based on the above publications, this study establishes a working framework for including organisational forgetting or loss in the study of absorptive capacity and the creation of competitive advantages. Specific reference has been made to the concept of organisational forgetting, loss or unlearning by a small group of academics (Prahalad & Bettis, 1986; Nystrom & Starbuck, 1984; Martin de Holan & Phillips, 2003), in most cases, without it being the main subject of the research. This investigation also uses as a starting point the studies conducted by Martin de Holan & Phillips (2003, 2004) and Fernandez & Sune (2009) investigating how and why organisational forgetting occurs.
Hydrologic Modelling

Advances in computational tools and modelling techniques combined with enhanced process knowledge have, in recent decades, facilitated a rapid progress in hydrologic modelling. From the use of traditional lumped models, the hydrologic science has moved to the much more complex, fully distributed models that exude an enhanced knowledge of hydrologic processes. Despite this progress, uncertainties in hydrologic predictions remain. The Indian contribution to hydrologic science literature in the recent years has been significant, covering areas of surface water, groundwater, climate change impacts and quantification of uncertainties. Future scientific efforts in hydrologic science in India are expected to involve better, more robust observation techniques and datasets, deeper process-knowledge at a range of spatio-temporal scales, understanding links between hydrologic and other natural and human systems, and integrated solutions using multidisciplinary approaches.
Interactions between serotypes of dengue highlight epidemiological impact of cross-immunity

Dengue, a mosquito-borne virus of humans, infects over 50 million people annually. Infection with any of the four dengue serotypes induces protective immunity to that serotype, but does not confer long-term protection against infection by other serotypes. The immunological interactions between serotypes are of central importance in understanding epidemiological dynamics and anticipating the impact of dengue vaccines. We analysed a 38-year time series with 12 197 serotyped dengue infections from a hospital in Bangkok, Thailand. Using novel mechanistic models to represent different hypothesized immune interactions between serotypes, we found strong evidence that infection with dengue provides substantial short-term cross-protection against other serotypes (approx. 1–3 years). This is the first quantitative evidence that short-term cross-protection exists since human experimental infection studies performed in the 1950s. These findings will impact strategies for designing dengue vaccine studies, future multi-strain modelling efforts, and our understanding of evolutionary pressures in multi-strain disease systems.
Laminin α4 Deficient Mice Exhibit Decreased Capacity for Adipose Tissue Expansion and Weight Gain

Obesity is a global epidemic that contributes to the increasing medical burdens related to type 2 diabetes, cardiovascular disease and cancer. A better understanding of the mechanisms regulating adipose tissue expansion could lead to therapeutics that eliminate or reduce obesity-associated morbidity and mortality. The extracellular matrix (ECM) has been shown to regulate the development and function of numerous tissues and organs. However, there is little understanding of its function in adipose tissue. In this manuscript we describe the role of laminin α4, a specialized ECM protein surrounding adipocytes, on weight gain and adipose tissue function. Adipose tissue accumulation, lipogenesis, and structure were examined in mice with a null mutation of the laminin α4 gene (Lama4−/ −) and compared to wild-type (Lama4+/+) control animals. Lama4−/ − mice exhibited reduced weight gain in response to both age and high fat diet. Interestingly, the mice had decreased adipose tissue mass and altered lipogenesis in a depot-specific manner. In particular, epididymal adipose tissue mass was specifically decreased in knock-out mice, and there was also a defect in lipogenesis in this depot as well. In contrast, no such differences were observed in subcutaneous adipose tissue at 14 weeks. The results suggest that laminin α4 influences adipose tissue structure and function in a depot-specific manner. Alterations in laminin composition offers insight into the roll the ECM potentially plays in modulating cellular behavior in adipose tissue expansion.
Effect of Different Cooking Methods on the Quality Attributes of Chicken Meat Cutlets

Present study was envisaged to assess the effect of various cooking methods viz. deep fat frying, oven cooking, air frying, and oven cooking followed by shallow frying for preparation of chicken meat cutlets. Three different treatments as per pre standardized formulations viz. Control, T1 (chicken meat cutlets with 30% meat emulsion) and T2 (with 3% refined wheat flour) were cooked by various cooking methods and subjected to various physico-chemical, instrumental colour and textural attributes, and sensory quality attributes. Under deep fat frying and oven cooking, cooking yield of treatments were recorded significantly (P<0.05) higher than control. Treatments scored better on various dimensional parameters such as increase in height, decrease in length and decrease in breadth irrespective of different cooking methods. The increase in height was recorded highest for T2 irrespective of cooking methods. The fat percent for T1 and T2 was recorded significantly (P<0.05) higher for deep fat frying (T1) and combination of oven and shallow frying. Flavour scores had been significantly (P<0.05) improved for T2, whereas T1 and C were comparable under different cooking methods. T2 showed significantly (P<0.05) higher overall acceptability scores than C and T1. Thus oven cooking followed by shallow frying was found optimum for preparation of chicken cutlets.
Adenine Enrichment at the Fourth CDS Residue in Bacterial Genes Is Consistent with Error Proofing for +1 Frameshifts

Abstract Beyond selection for optimal protein functioning, coding sequences (CDSs) are under selection at the RNA and DNA levels. Here, we identify a possible signature of “dual-coding,” namely extensive adenine (A) enrichment at bacterial CDS fourth sites. In 99.07% of studied bacterial genomes, fourth site A use is greater than expected given genomic A-starting codon use. Arguing for nucleotide level selection, A-starting serine and arginine second codons are heavily utilized when compared with their non-A starting synonyms. Several models have the ability to explain some of this trend. In part, A-enrichment likely reduces 5′ mRNA stability, promoting translation initiation. However T/U, which may also reduce stability, is avoided. Further, +1 frameshifts on the initiating ATG encode a stop codon (TGA) provided A is the fourth residue, acting either as a frameshift “catch and destroy” or a frameshift stop and adjust mechanism and hence implicated in translation initiation. Consistent with both, genomes lacking TGA stop codons exhibit weaker fourth site A-enrichment. Sequences lacking a Shine–Dalgarno sequence and those without upstream leader genes, that may be more error prone during initiation, have greater utilization of A, again suggesting a role in initiation. The frameshift correction model is consistent with the notion that many genomic features are error-mitigation factors and provides the first evidence for site-specific out of frame stop codon selection. We conjecture that the NTG universal start codon may have evolved as a consequence of TGA being a stop codon and the ability of NTGA to rapidly terminate or adjust a ribosome.
Long‐term disadvantages of selective root placement: root proliferation and shoot biomass of two perennial grass species in a 2‐year experiment

1 The long‐term benefits of root foraging in heterogeneous environments are unclear. The short duration of many previous studies may have overlooked the effects of patch depletion and root turnover, which may limit the long‐term rewards of root foraging for perennial plants. 2 The benefits of root foraging were investigated for Holcus lanatus and Nardus stricta over two growing seasons. Shoot biomass of each species was measured in homogeneous nutrient‐rich and nutrient‐poor treatments and in a heterogeneous treatment consisting of a nutrient‐rich and a nutrient‐poor side, at a high and a low overall level of nutrient availability at the same patch contrast. Large initial differences in nitrate concentrations in the soil solution between the soil types disappeared so that, after several months, nitrate levels were low in all soil types. 3 In heterogeneous treatments, Holcus was able to proliferate roots in the nutrient‐rich side compared with the nutrient‐poor side, but only at the high overall level of nutrient availability. Nardus did not selectively place roots in the nutrient‐rich side of the heterogeneous treatment at either nutrient level. 4 Root longevity, as determined by minirhizotron observations, revealed that roots of Holcus tended to be shorter lived than those of Nardus, and to live longer in nutrient‐poor soils. 5 Initially, Holcus produced more shoot biomass in the heterogeneous treatments, at both overall levels of nutrient availability, than expected from values in the homogeneous treatments, but this advantage disappeared by the end of the first growing season and, after 2 years, shoot biomass in the heterogeneous treatments was much less than expected. At the high overall level of nutrient availability, Holcus shoot biomass was not significantly greater than that produced in the homogeneous nutrient‐poor treatment. In contrast, shoot biomass of Nardus in the heterogeneous treatment was similar to the expected value, both after the first and second growing seasons. 6 For Holcus, fast root proliferation and presumably a high nutrient uptake resulted in increased shoot biomass in the short term, but this was then curtailed by rapid patch depletion and high losses due to a limited root life span. We discuss the implications for the long‐term rewards of root proliferation in perennial species of heterogeneous environments.
Restoration of Nontarget Species: Bee Communities and Pollination Function in Riparian Forests

Nontarget species such as pollinators may be of great importance to the restoration process and the long‐term functioning of restored habitats, but little is known about how such groups respond to habitat restoration. I surveyed bee communities at five equal‐aged restored sites, paired with five reference sites (riparian remnants) along the Sacramento River, California, United States. Flower availability and bee visitation patterns were also measured to examine the restoration of pollination function. Restoration of structural vegetation allowed diverse and abundant native bee communities to establish at the restoration sites; however, the composition of these important pollinator communities was distinct from that in the remnant riparian sites. Differences did not arise primarily from differences in the composition of the flowering‐plant community; rather there must be other physical characteristics of the restored sites or differences in nesting site availability that led to the different pollinator communities. Because sites were spatially paired, the differences are unlikely to be driven by landscape context. Bee life‐history and other biological traits may partially explain the differences between bee communities at restored and remnant sites. Patterns of visitation to native plant species suggest that pollination function is restored along with pollinator abundance and richness; however, function may be less robust in restored habitats. An examination of interaction networks between bees and plant species found at both restored and remnant riparian sites showed less redundancy of pollinators visiting some plants at restored habitats.
UvA-DARE ( Digital Academic Repository ) Microfoundations of partnerships : exploring the role of employees in trickle effects

The growing body of literature on partnerships has paid most attention to their implications at the macro level, for society, as well as the meso level, for the partnering organisations. While generating many valuable insights, what has remained underexposed is the micro level, i.e. the role of managers and employees in partnerships, and how their actions and interactions can have an effect on the spread and potential effectiveness of collaborative efforts. This article uses a case-study approach to empirically explore the patterns and potential boundary conditions of so-called ‘trickle effects’ of partnerships among individual actors within and outside partnering companies, which have thus far only been proposed conceptually. Based on interviews with employees from three different companies, we found an evidence of trickle-down and trickle-up effects with higher and lower management, as well as trickle-round effects with colleagues, family, friends and customers. The article discusses several partnership characteristics that seem to play a role, and notes implications for research and practice.
Comparing the Health Effects of Ambient Particulate Matter Estimated Using Ground-Based versus Remote Sensing Exposure Estimates

Background: Remote sensing (RS) is increasingly used for exposure assessment in epidemiological and burden of disease studies, including those investigating whether chronic exposure to ambient fine particulate matter (PM2.5) is associated with mortality. Objectives: We compared relative risk estimates of mortality from diseases of the circulatory system for PM2.5 modeled from RS with that for PM2.5 modeled using ground-level information. Methods: We geocoded the baseline residence of 668,629 American Cancer Society Cancer Prevention Study II (CPS-II) cohort participants followed from 1982 to 2004 and assigned PM2.5 levels to all participants using seven different exposure models. Most of the exposure models were averaged for the years 2002–2004, and one RS estimate was for a longer, contemporaneous period. We used Cox proportional hazards regression to estimate relative risks (RRs) for the association of PM2.5 with circulatory mortality and ischemic heart disease. Results: Estimates of mortality risk differed among exposure models. The smallest relative risk was observed for the RS estimates that excluded ground-based monitors for circulatory deaths [RR = 1.02, 95% confidence interval (CI): 1.00, 1.04 per 10 μg/m3 increment in PM2.5]. The largest relative risk was observed for the land-use regression model that included traffic information (RR = 1.14, 95% CI: 1.11, 1.17 per 10 μg/m3 increment in PM2.5). Conclusions: We found significant associations between PM2.5 and mortality in every model; however, relative risks estimated from exposure models using ground-based information were generally larger than those estimated using RS alone. Citation: Jerrett M, Turner MC, Beckerman BS, Pope CA III, van Donkelaar A, Martin RV, Serre M, Crouse D, Gapstur SM, Krewski D, Diver WR, Coogan PF, Thurston GD, Burnett RT. 2017. Comparing the health effects of ambient particulate matter estimated using ground-based versus remote sensing exposure estimates. Environ Health Perspect 125:552–559; http://dx.doi. org/10.1289/EHP575
X-Ray Phase-Contrast CT of a Pancreatic Ductal Adenocarcinoma Mouse Model

To explore the potential of grating-based x-ray phase-contrast computed tomography (CT) for preclinical research, a genetically engineered mouse model of pancreatic ductal adenocarcinoma (PDAC) was investigated. One ex-vivo mouse specimen was scanned with different grating-based phase-contrast CT imaging setups covering two different settings: i) high-resolution synchrotron radiation (SR) imaging and ii) dose-reduced imaging using either synchrotron radiation or a conventional x-ray tube source. These experimental settings were chosen to assess the potential of phase-contrast imaging for two different types of application: i) high-performance imaging for virtual microscopy applications and ii) biomedical imaging with increased soft-tissue contrast for in-vivo applications. For validation and as a reference, histological slicing and magnetic resonance imaging (MRI) were performed on the same mouse specimen. For each x-ray imaging setup, attenuation and phase-contrast images were compared visually with regard to contrast in general, and specifically concerning the recognizability of lesions and cancerous tissue. To quantitatively assess contrast, the contrast-to-noise ratios (CNR) of selected regions of interest (ROI) in the attenuation images and the phase images were analyzed and compared. It was found that both for virtual microscopy and for in-vivo applications, there is great potential for phase-contrast imaging: in the SR-based benchmarking data, fine details about tissue composition are accessible in the phase images and the visibility of solid tumor tissue under dose-reduced conditions is markedly superior in the phase images. The present study hence demonstrates improved diagnostic value with phase-contrast CT in a mouse model of a complex endogenous cancer, promoting the use and further development of grating-based phase-contrast CT for biomedical imaging applications.