Miracle-dz/UniFAR-FTUs huggingface dataset:
Enabling T Cell Recruitment to Tumours as a Strategy for Improving Adoptive T Cell Therapy

I mmunotherapy has successfully been implemented as the standard of care in a number of oncologic indications. A hallmark of cancer immunotherapy is the successful activation of T cells against cancer cells, leading to unparalleled efficacy for some tumour entities. However, current approved approaches are not specific, limiting both their activity and their safety. A more tailored way of using the therapeutic potential of T cells is adoptive T cell therapy, which encompasses ex vivo T cell manipulation and reinfusion to patients suffering from cancer. In haematologic malignancies such as acute lymphatic leukaemia of the B cell lineage, T cells modified with a chimeric antigen receptor against the B cell lineage antigen CD19 induce remissions in a high proportion of patients. In contrast, patients suffering from advanced solid tumours have shown little benefit from cell-based approaches. This is partly due to limited access of T cells to the tumour tissue, consequently restricting T cell activity. In this review, we focus on the limitations of T cell trafficking towards solid tumours. We summarise the existing knowledge on lymphocyte migration to understand how this pathway may be used to open therapeutic approaches for a broader range of indications. We also review new strategies targeting the tumour site that aid naturally occurring or gene-engineered T cells to migrate to solid tumours. Finally, we discuss how guiding T cells towards the tumour might contribute in harnessing their full cytolytic potential.
The effect of vasodilator &bgr;-blockers on renal function in hypertensive patients

Background: Not only is there a limited number of studies on the effects of vasodilator &bgr;-blocker (VBB) therapy on kidney function – specifically, glomerular filtration rate (GFR), serum creatinine (sCr) and proteinuria – but of those that have been reported, the results are mixed. This meta-analysis seeks to assess the efficacy of VBBs on selected renal parameters in hypertensive patients. Methods: We conducted a meta-analysis of any prospective trial that provided both baseline and follow-up of at least 4 weeks of VBB therapy – carvedilol, labetalol, dilevalol, nebivolol and celiprolol in patients with hypertension. We used Ovid MEDLINE, EMBASE and PubMed, all without date restrictions. We included 39 studies totaling 3987 patients. Results: Although VBBs did not significantly change GFR or sCr levels after at least 4 weeks of therapy, they did significantly decrease protein excretion by −0.12 SD units [95% confidence interval (CI) −0.19 to −0.04; P < 0.01]. VBBs did not alter renal blood or plasma flow, but renal vascular resistance (RVR) decreased by −20.03 mmHg min/l (95% CI −28.92 to −11.15; P < 0.01). In the analysis which compared VBBs with non-VBBs, the only significant difference was the greater decrease in RVR in the VBB group by −38.44 mmHg min/l (95% CI −60.57 to −16.31; P < 0.01). Conclusion: VBBs do not affect GFR or sCr levels, but decrease protein excretion. This class of &bgr;-blockers, however, is not superior to non-VBBs in reducing proteinuria. VBBs decrease RVR significantly more than non-VBBs.
Anxiety levels in clinically referred children and their parents: examining the unique influence of self-reported attachment styles and interview-based reflective functioning in mothers and fathers.

OBJECTIVE Although much is known about childhood anxiety disorders, the differential contributions by mothers and fathers to child anxiety is poorly understood. This study examined the relation between child anxiety and parental level of psychopathology, attachment style, and reflective functioning (RF). DESIGN Thirty-eight clinically anxious children aged 7-12 years (55.3% female) referred for treatment and their parents (37 mothers, 34 fathers) participated in the study. METHOD Reflective functioning was coded based on Adult Attachment Interviews. Self-report questionnaires on attachment and psychopathology were administered. RESULTS Paternal psychopathology, attachment avoidance, and attachment anxiety as well as maternal attachment anxiety were associated with child anxiety. Mothers had higher RF abilities than fathers. Lower levels of RF in mothers and higher levels of attachment avoidance in fathers explained 42% of the variance in anxiety levels of the child. CONCLUSION Mothers and fathers may provide unique contributions to the development of child anxiety. The findings highlight the importance of considering fathers as well as mothers in research and treatment for childhood anxiety disorders.
Intraspecific variation in traits reduces ability of trait‐based models to predict community structure

Questions Is it possible to predict the composition of local plant assemblages? Trait-based approaches have offered some promise, especially in cases where deterministic processes such as environmental filtering and niche differentiation shape communities. In this study, we asked how much intraspecific variation contributes to trait distributions within and among plant communities, and whether trait distributions resulting from environmental filtering and niche differentiation can predict accurately the relative species abundances of montane plant species in local communities. Location West Elk Mountains, Colorado, USA. Methods We collected functional trait, species composition, and environmental data from 14 sites along a broad climate gradient in Colorado, USA ranging in elevation from 2480 to 3560 m. We partitioned the variation within and among sites into intraspecific and interspecific components, and compared the results to values from a recent global meta-analysis which examined intraspecific trait variability patterns. We also used these data to parameterize statistical models that have been shown to reproduce patterns associated with the processes of environmental filtering and niche differentiation. We fit two models to the data, one assuming that niche differentiation is invariant among sites, and another assuming that niche differentiation varies among sites. Results and Conclusion We found that the trait-based models performed worse at predicting species relative abundances in local communities than did a null model assuming equal abundances of all species. One plausible explanation for the poor performance of the models is that intraspecific variation in functional traits, which in our system was higher than the global averages documented in the meta-analysis, swamped the effects of interspecific variation in functional traits along the climatic gradient. In particular, almost all variation in root traits was within rather than among species, even among sites. Our results suggest that a greater focus be placed on measuring intraspecific trait variability and determining its consequences for community assembly and ecosystem properties. This article is protected by copyright. All rights reserved.
Comparative Structural Analysis of the Erbin PDZ Domain and the First PDZ Domain of ZO-1

We report a structural comparison of the first PDZ domain of ZO-1 (ZO1-PDZ1) and the PDZ domain of Erbin (Erbin-PDZ). Although the binding profile of Erbin-PDZ is extremely specific ([D/E][T/S]WVCOOH), that of ZO1-PDZ1 is similar ([R/K/S/T][T/S][W/Y][V/I/L]COOH) but broadened by increased promiscuity for three of the last four ligand residues. Consequently, the biological function of ZO-1 is also broadened, as it interacts with both tight and adherens junction proteins, whereas Erbin is restricted to adherens junctions. Structural analyses reveal that the differences in specificity can be accounted for by two key differences in primary sequence. A reduction in the size of the hydrophobic residue at the base of the site0 pocket enables ZO1-PDZ1 to accommodate larger C-terminal residues. A single additional difference alters the specificity of both site-1 and site-3. In ZO1-PDZ1, an Asp residue makes favorable interactions with both Tyr-1 and Lys/Arg-3. In contrast, Erbin-PDZ contains an Arg at the equivalent position, and this side chain cannot accommodate either Tyr-1 or Lys/Arg-3 but, instead, interacts favorably with Glu/Asp-3. We propose a model for ligand recognition that accounts for interactions extending across the entire binding site but that highlights several key specificity switches within the PDZ domain fold.
Climatic niche breadth and species richness in temperate treefrogs

Patterns of species richness are often closely linked with climate, but the specific mechanisms by which species' climatic niches underlie large‐scale richness patterns remain poorly understood. It has been hypothesized that reduced temperature seasonality in the tropics promotes the evolution of species with narrow temperature niche breadths, and that this hypothesis helps explain high tropical richness. However, the relationship between species' climatic niche breadths and species richness has yet to be tested. We have addressed this issue using treefrogs (Hylidae) in eastern North America.
Variables Associated with Chondral and Meniscal Injuries in Anterior Cruciate Ligament Surgery

Abstract This article aims to evaluate factors associated with chondral and meniscal lesions in primary and revision anterior cruciate ligament (ACL) reconstructions. ACL reconstructions from 2001 to 2008 at a single institution were retrospectively analyzed. Logistic regression was used to estimate the association between chondral and meniscal injuries and age, gender, tear chronicity, additional ligamentous injuries, sport type, and participation level. Of the 3,040 ACL reconstructions analyzed, 90.4% were primary reconstructions and 9.6% were revisions. Meniscal injuries were significantly lower in the revision group (44.0 vs. 51.9%; p = 0.01), while chondral injuries were significantly higher in the revision group (39.9 vs. 24.0%; p < 0.0001). Inspection of the small subgroup (n = 85) receiving both primary and revision ACL surgery at our center indicated that meniscal injuries at revision were evenly split between menisci with and without previous repairs, whereas the vast majority of Grade III and IV chondral lesions were new. More patients presented for surgery later in the revision group than in the primary group (56.5 vs. 35.3%; p < 0.0001). Male gender, primary reconstruction, and short interval (less than 2 weeks) between injury and surgery were associated with increased likelihood of meniscus tear. Age (greater than 22 years) and long interval (greater than 6 weeks) between injury to surgery and higher sport activity level were associated with chondral lesions. Revision ACL reconstructions are associated with a higher proportion of chondral lesions and a lower proportion of meniscal tears. Early primary and revision ACL construction is recommended to reduce the probability of chondral lesions.
Targeted agri‐environment schemes significantly improve the population size of common farmland bumblebee species

Changes in agricultural practice across Europe and North America have been associated with range contractions and local extinction of bumblebees (Bombus spp.). A number of agri‐environment schemes have been implemented to halt and reverse these declines, predominantly revolving around the provision of additional forage plants. Although it has been demonstrated that these schemes can attract substantial numbers of foraging bumblebees, it remains unclear to what extent they actually increase bumblebee populations. We used standardized transect walks and molecular techniques to compare the size of bumblebee populations between Higher Level Stewardship (HLS) farms implementing pollinator‐friendly schemes and Entry Level Stewardship (ELS) control farms. Bumblebee abundance on the transect walks was significantly higher on HLS farms than ELS farms. Molecular analysis suggested maximum foraging ranges of 566 m for Bombus hortorum, 714 m for B. lapidarius, 363 m for B. pascuorum and 799 m for B. terrestris. Substantial differences in maximum foraging range were found within bumblebee species between farm types. Accounting for foraging range differences, B. hortorum (47 vs 13 nests/km2) and B. lapidarius (45 vs 22 nests/km2) were found to nest at significantly greater densities on HLS farms than ELS farms. There were no significant differences between farm type for B. terrestris (88 vs 38 nests/km2) and B. pascuorum (32 vs 39 nests/km2). Across all bumblebee species, HLS management had a significantly positive effect on bumblebee nest density. These results show that targeted agri‐environment schemes that increase the availability of suitable forage can significantly increase the size of wild bumblebee populations.
The Role of Autonomy Support and Motivation in the Prediction of Interest and Dropout Intentions in Sport and Education Settings

Based on the hierarchical model of intrinsic and extrinsic motivation (Vallerand, 1997), the purpose of the present research was to propose and test a model that posits that individuals’ perceptions of autonomy support from their supervisor in an activity (e.g., coach, teacher) and their global autonomous motivation jointly promote their autonomous (contextual) motivation toward the activity. In turn, contextual autonomous motivation positively predicts interest in the activity, whereas it negatively predicts intentions to drop out of the activity. In Study 1, the model was tested with a sample of 206 competitive athletes registered in the French Skiing Federation. In Study 2, a short longitudinal design was used, and the sample was composed of 206 French high school students (128 female, 78 male). Results from structural equation modeling analyses supported the hypothesized model. These results provided support for the hierarchical model of intrinsic and extrinsic motivation (Vallerand, 1997). The implications of the findings and future research avenues are discussed in light of the hierarchical model and self-determination theory.
Relationship between Credit Rating, Capital Structure and Earning Management Behaviour: Evidence from Pakistani Listed Firms

Credit ratings have become a widely accepted measure of firms’ creditworthiness in financial markets. The present study aims to examine the impact of external credit ratings on the financial structure decision - making of Pakistani non - financial firms for the period 2007-2012 This study examines whether there are any systematic differences in firms’ levels of leverage across the rating levels which would suggest that the cost and benefits of credit ratings are material for such firms. The study finds that credit ratings are an important determinant of the capital structures of firms and that there is a non-linear inverted U-shaped relationship between credit ratings and capital structures. It is noted that rated firms have higher leverage than non-rated firms, but within the rated firms, leverage varies across the rating levels. High and low rated firms are found to have low leverage in their capital structures, and mid rated firms have higher leverage. Low gearing ratios may suggest that such firms have higher incentive to maintain their current ratings or to achieve upgrades, given the cost and benefits offered by credit ratings, than firms with high gearing ratios. While credit rating play a significant role in explaining why firm involve in managing their earning and it is found that rated firm manage their earning in a significantly different way as compared to the non-rated firms and it is also found that firm at the end of the rating spectrum manage their earning to the greater extent as compared to the mid rated firm. The implication of the study is that firms having higher and lower ratings have low level of leverage and mid rated firms have higher level of leverage. Previous year ratings provokes firms to indulge in earning smoothening activates and rating agencies needs to consider this factor while making their final valuation of the firm
On the Adequacy of the Transmission Line Model to Describe the Graphene–Metal Contact Resistance

The contact-end-resistance (CER) method is applied to transfer length method structures to characterize in-depth the graphene–metal contact and its dependence on the back-gate bias. Parameters describing the graphene–metal stack resistance are extracted through the widely used transmission line model. The results show inconsistencies which highlight application limits of the model underlying the extraction method. These limits are attributed to the additional resistance associated with the p-p+ junction located at the contact edge, that is not part of the conventional transmission line model. Useful guidelines for a correct application of the extraction technique are provided, identifying the bias range in which this additional resistance is negligible. Finally, the CER method and the transmission line model are exploited to characterize the graphene–metal contacts featuring different metals.
Next Generation Breeding in Potato

Potato is the world's number one non-grain commodity and ranks at fourth position after maize, rice and wheat. As a species, potato is very docile to cell culture, it also contains an extended history of applications in the field of biotechnology for the improvement of crops. The genomic insurgency from the recent past has significantly enhanced the overall knowhow of the genetic structure of all the crops. Crop genome sequences has totally reformed our view and understanding for genome association and genome development. Increased knowledge in markers along with the advanced phenotyping, genotyping by sequencing, genomewide association studies added a new way for determining marker-trait associations that can withstand genome based breeding programs. Accessibility of sequencing of genomic data has permitted editing of genome (localized mutagenesis), for obtaining sequences of gene that is anticipated by the breeders. To develop some genetic maps, markers application and genomics in the field of potato breeding these genetic characteristics have also assigned the tasks to the breeders. Many strategies are formulated to describe the potato loci, (contender) genes and alleles, and association of genotype with the phenotype are also stated. This review demonstrates how next generation phenotyping, genome-wide association studies and genome editing tools can be used to modify tools to genomics for the need of potato breeders to transform potato improvement.
Organizational Factors Affecting Propensity to Adopt Cloud Computing

Cloud computing (CC) is emerging as a new paradigm of ICT resources acquisition and management by firms. This paper empirically investigates and compares the effects of a set of organizational factors on the propensity to adopt CC, based on data from 676 European firms from the glass, ceramics and cement industries, collected through the e-Business Watch Survey of the European Commission. Our results do not confirm the initial expectations that CC would be adopted primarily by the SMEs, as they indicate that the size has a positive effect on the propensity to adopt CC. Furthermore, we have found that the latter is associated with ICT investment reduction strategy (quite usual today due to the existing economic crisis), and only to a lower extent with innovation oriented strategy. Our results also indicate that previous experience of ICT outsourcing and employment of ICT specialized personnel have positive effects on the propensity to adopt CC. Finally, we have found that firms with higher ICT infrastructure sophistication have higher CC adoption propensity.
Photonics and Transport in Bulk Heterojunction Organic Solar Cells

JOHN R. TUMBLESTON: Photonics and Transport in Bulk Heterojunction Organic Solar Cells. (Under the direction of Rene Lopez.) In this thesis, the groundwork is established for a new type of bulk heterojunction (BHJ) organic solar cell geometry that has photonic crystal (PC) photoactive layers. This design is motivated by the need to improve light absorption without increasing active layer thickness, which for many BHJ systems, degrades electrical performance. It is demonstrated that with the right choice of materials and cell dimensions, quasiguided or resonant modes are excited near the band edge of a variety of BHJ blends to enhance absorption. Resonant modes are predicted by first developing a scattering matrix optical model and then observed in wavelength-, polarization-, and angular-dependent reflection and photocurrent measurements. PC cells are fabricated using a facile nanopatterning technique, where highly ordered arrays of submicron features are constructed over large areas in a single step. Optical and electrical function of this new cell architecture is fully explored in this thesis. Through optical measurements and modeling, PC devices show clear enhancements in light absorption. On the other hand, the impact of the nonplanar geometry on electrical performance is not as easily deduced due to the multitude of electrical processes that lead to photocurrent generation. First, the electrical properties of the electron transporting layer that interfaces with the BHJ nanopattern and provides optical contrast in the PC greatly affect parasitic resistances in the solar cell. By including resistance losses in a drift/diffusion numerical model that describes electrical performance, it is shown that these losses greatly influence fundamental steps leading to photocurrent generation. This is confirmed with experiment by comparing two BHJ material systems that have different affinities for exciton separation. Second, significant levels of free carrier recombination are predicted by the electro-optical model due to the relatively long transport paths in the nanopattern features. To test this prediction, an experimental technique is developed to measure the transport lengths of photogenerated electrons and holes in BHJ solar cells. It is found that transport lengths of positive and negative carriers are mismatched and helps explain both PC electrical performance and recent conflicting results of planar BHJ solar cells in the literature.
Bearing-Opportunistic Network Coding

This paper presents a novel, practical, routing-independent networkcoding algorithm: BON-Bearing opportunistic network coding. Simplicity is its main benefit as it introduces little overhead to the network since nodes do not need to keep track of received traffic for their neighbouring nodes. Algorithm makes coding decisions based solely on the information about the packet previous and next hop node position. Algorithm functions between the MAC and link layers, with small modifications made only to the MAC layer. Using different topologies and different traffic loads and distributions in the simulation model we evaluated algorithm performance and compared it to a well-known COPE algorithm.
Small-scale spatial variation in rates of metacercarial accumulation by a bivalve second intermediate host

In a field experiment, the accumulation of trematode (Echinostomatidae) metacercariae by the New Zealand cockle Austrovenus stutchburyi was compared among treatments with different seabed hydrodynamics and sedimentation rates. There was no significant difference among the treatments in the rate at which cockles accumulated metacercariae, suggesting that infection rates are not influenced by water flow conditions within the normal range experienced in natural habitats. There was, however, substantial spatial variation in infection rates among the experimental plots. This result indicates that metacercarial accumulation varies horizontally as well as vertically within the intertidal zone.