p53 status correlates with histopathological response in patients with soft tissue sarcomas treated using isolated limb perfusion with TNF-α and melphalan

Background: Recombinant tumor necrosis factor-α (TNF-α) combined to melphalan is clinically administered through isolated limb perfusion (ILP) for regionally advanced soft tissue sarcomas of the limbs. In preclinical studies, wild-type p53 gene is involved in the regulation of cytotoxic action of TNF-α and loss of p53 function contributes to the resistance of tumour cells to TNF-α. The relationship between p53 status and response to TNF-α and melphalan in patients undergoing ILP is unknown. Patients and methods: We studied 110 cases of unresectable limbs sarcomas treated by ILP. Immunohistochemistry was carried out using DO7mAb, which reacts with an antigenic determinant from the N-terminal region of both the wild-type and mutant forms of the p53 protein, and PAb1620mAb, which reacts with the 1620 epitope characteristic of the wild-type native conformation of the p53 protein. The immunohistochemistry data were then correlated with various clinical parameters. Results: P53DO7 was found expressed at high levels in 28 patients, whereas PAb1620 was negative in 20. The tumours with poor histological response to ILP with TNF-α and melphalan showed significantly higher levels of p53-mutated protein. Conclusions: Our results might be a clue to a role of p53 protein status in TNF-α and melphalan response in clinical us

The Effect of Volitional Preemptive Abdominal Contraction on Biomechanical Measures During A Front Versus Back Loaded Barbell Squat

# Background Weightlifting is growing in popularity among recreational and competitive athletes. The barbell back squat (BackS) is commonly included in these training programs, while the barbell front squat (FrontS) is commonly performed as a component of other lifts such as the power clean or clean and jerk, it is less commonly practiced in isolation. # Hypothesis/Purpose The purpose of this study was to examine the effects of VPAC performance on trunk muscle and LE biomechanical responses during loaded BackS versus FrontS in healthy subjects. # Study Design Controlled Laboratory Study # Methods Healthy male subjects with the ability to perform a sub-maximal loaded barbell squat lift were recruited. Subjects completed informed consent, demographic/medical history questionnaires and an instructional video. Subjects practiced VPAC and received feedback. Surface electromyography (sEMG) electrodes and kinematic markers were applied. Muscles included were the internal oblique (IO), external oblique (EO), rectus abdominis, iliocostalis lumborum (ICL), superficial multifidi, rectus femoris, vastus lateralis, biceps femoris, and gluteus maximus. Maximal voluntary isometric contractions established reference sEMG values. A squat one-rep-max (1RM) was predicted by researchers using a three to five repetition maximum (3RM, 5RM) load protocol. Subjects performed BackS trials at 75% 1RM while FrontS trials were performed at 75% BackS weight, both with and without VPAC. Subjects performed three repetitions of each condition with feet positioned on two adjacent force plates. Significant interactions and main effects were tested using a 2(VPAC strategy) x 2(squat variation) and 2(VPAC strategy) x 2(direction) within-subject repeated measures ANOVAs. Tukey's Post-Hoc tests identified the location of significant differences. # Results Trunk muscle activity was significantly higher during FrontS versus BackS regardless of VPAC condition. (IO: p=0.018, EO: p\<0.001, ICL: p\<0.001) VPAC increased performance time for both squat variations (p=.0011), which may be associated with decreased detrimental force potential on the lumbar spine and knees. VPAC led to improved ability to maintain a neutral lumbar spine during both squat variations. This finding is associated with decreased detrimental force potential on the lumbar spine. # Conclusions Findings could help guide practitioners and coaches to choose squat variations and incorporate VPAC strategies during their treatments and/or training programs. # Level of Evidence Level 3 ©The Author(s

Satellite and in situ observations for advancing global Earth surface modelling: a review

In this paper, we review the use of satellite-based remote sensing in combination with in situ data to inform Earth surface modelling. This involves verification and optimization methods that can handle both random and systematic errors and result in effective model improvement for both surface monitoring and prediction applications. The reasons for diverse remote sensing data and products include (i) their complementary areal and temporal coverage, (ii) their diverse and covariant information content, and (iii) their ability to complement in situ observations, which are often sparse and only locally representative. To improve our understanding of the complex behavior of the Earth system at the surface and sub-surface, we need large volumes of data from high-resolution modelling and remote sensing, since the Earth surface exhibits a high degree of heterogeneity and discontinuities in space and time. The spatial and temporal variability of the biosphere, hydrosphere, cryosphere and anthroposphere calls for an increased use of Earth observation (EO) data attaining volumes previously considered prohibitive. We review data availability and discuss recent examples where satellite remote sensing is used to infer observable surface quantities directly or indirectly, with particular emphasis on key parameters necessary for weather and climate prediction. Coordinated high-resolution remote-sensing and modelling/assimilation capabilities for the Earth surface are required to support an international application-focused effort

The International Soil Moisture Network:Serving Earth system science for over a decade

In 2009, the International Soil Moisture Network (ISMN) was initiated as a community effort, funded by the European Space Agency, to serve as a centralised data hosting facility for globally available in situ soil moisture measurements (Dorigo et al., 2011b, a). The ISMN brings together in situ soil moisture measurements collected and freely shared by a multitude of organisations, harmonises them in terms of units and sampling rates, applies advanced quality control, and stores them in a database. Users can freely retrieve the data from this database through an online web portal (https://ismn.earth/en/, last access: 28 October 2021). Meanwhile, the ISMN has evolved into the primary in situ soil moisture reference database worldwide, as evidenced by more than 3000 active users and over 1000 scientific publications referencing the data sets provided by the network. As of July 2021, the ISMN now contains the data of 71 networks and 2842 stations located all over the globe, with a time period spanning from 1952 to the present. The number of networks and stations covered by the ISMN is still growing, and approximately 70 % of the data sets contained in the database continue to be updated on a regular or irregular basis. The main scope of this paper is to inform readers about the evolution of the ISMN over the past decade, including a description of network and data set updates and quality control procedures. A comprehensive review of the existing literature making use of ISMN data is also provided in order to identify current limitations in functionality and data usage and to shape priorities for the next decade of operations of this unique community-based data repository

Hyperresolution information and hyperresolution ignorance in modelling the hydrology of the land surface

There is a strong drive towards hyperresolution earth system models in order to resolve finer scales of motion in the atmosphere. The problem of obtaining more realistic representation of terrestrial fluxes of heat and water, however, is not just a problem of moving to hyperresolution grid scales. It is much more a question of a lack of knowledge about the parameterisation of processes at whatever grid scale is being used for a wider modelling problem. Hyperresolution grid scales cannot alone solve the problem of this hyperresolution ignorance. This paper discusses these issues in more detail with specific reference to land surface parameterisations and flood inundation models. The importance of making local hyperresolution model predictions available for evaluation by local stakeholders is stressed. It is expected that this will be a major driving force for improving model performance in the future. Keith BEVEN, Hannah CLOKE, Florian PAPPENBERGER, Rob LAMB, Neil HUNTE

Global snow mass measurements and the effect of stratigraphic detail on inversion of microwave brightness temperatures

Snow provides large seasonal storage of freshwater, and information about the distribution of snow mass as Snow Water Equivalent (SWE) is important for hydrological planning and detecting climate change impacts. Large regional disagreements remain between estimates from reanalyses, remote sensing and modelling. Assimilating passive microwave information improves SWE estimates in many regions but the assimilation must account for how microwave scattering depends on snow stratigraphy. Physical snow models can estimate snow stratigraphy, but users must consider the computational expense of model complexity versus acceptable errors. Using data from the National Aeronautics and Space Administration Cold Land Processes Experiment (NASA CLPX) and the Helsinki University of Technology (HUT) microwave emission model of layered snowpacks, it is shown that simulations of the brightness temperature difference between 19 GHz and 37 GHz vertically polarised microwaves are consistent with Advanced Microwave Scanning Radiometer-Earth Observing System (AMSR-E) and Special Sensor Microwave Imager (SSM/I) retrievals once known stratigraphic information is used. Simulated brightness temperature differences for an individual snow profile depend on the provided stratigraphic detail. Relative to a profile defined at the 10 cm resolution of density and temperature measurements, the error introduced by simplification to a single layer of average properties increases approximately linearly with snow mass. If this brightness temperature error is converted into SWE using a traditional retrieval method then it is equivalent to ±13 mm SWE (7% of total) at a depth of 100 cm. This error is reduced to ±5.6 mm SWE (3 % of total) for a two-layer model

Edible bio-based nanostructures: delivery, absorption and potential toxicity

The development of bio-based nanostructures as nanocarriers of bioactive compounds to specific body sites has been presented as a hot topic in food, pharmaceutical and nanotechnology fields. Food and pharmaceutical industries seek to explore the huge potential of these nanostructures, once they can be entirely composed of biocompatible and non-toxic materials. At the same time, they allow the incorporation of lipophilic and hydrophilic bioactive compounds protecting them against degradation, maintaining its active and functional performance. Nevertheless, the physicochemical properties of such structures (e.g., size and charge) could change significantly their behavior in the gastrointestinal (GI) tract. The main challenges in the development of these nanostructures are the proper characterization and understanding of the processes occurring at their surface, when in contact with living systems. This is crucial to understand their delivery and absorption behavior as well as to recognize potential toxicological effects. This review will provide an insight into the recent innovations and challenges in the field of delivery via GI tract using bio-based nanostructures. Also, an overview of the approaches followed to ensure an effective deliver (e.g., avoiding physiological barriers) and to enhance stability and absorptive intestinal uptake of bioactive compounds will be provided. Information about nanostructures potential toxicity and a concise description of the in vitro and in vivo toxicity studies will also be given.Joana T. Martins, Oscar L. Ramos, Ana C. Pinheiro, Ana I. Bourbon, Helder D. Silva and Miguel A. Cerqueira (SFRH/BPD/89992/2012, SFRH/BPD/80766/2011, SFRH/BPD/101181/2014, SFRH/BD/73178/2010, SFRH/BD/81288/2011, and SFRH/BPD/72753/2010, respectively) are the recipients of a fellowship from the Fundacao para a Ciencia e Tecnologia (FCT, POPH-QREN and FSE, Portugal). The authors thank the FCT Strategic Project PEst-OE/EQB/LA0023/2013 and the project "BioInd-Biotechnology and Bioengineering for improved Industrial and Agro-Food processes," REF.NORTE-07-0124-FEDER-000028, co-funded by the Programa Operacional Regional do Norte (ON.2-O Novo Norte), QREN, FEDER. We also thank to the European Commission: BIOCAPS (316265, FP7/REGPOT-2012-2013.1) and Xunta de Galicia: Agrupamento INBIOMED (2012/273) and Grupo con potencial de crecimiento. The support of EU Cost Action FA1001 is gratefully acknowledged

Global Soil Moisture Patterns Observed by Space Borne Microwave Radiometers and Scatterometers

Within the scope of the upcoming launch of a new water related satellite mission (SMOS) a global evaluation study was performed on two available global soil moisture products. ERS scatterometer surface wetness data was compared to AMSR-E soil moisture data. This study pointed out a strong similarity between both products in sparse to moderate vegetated regions with an average correlation coefficient of 0.83. Low correlations were found in densely vegetated areas and deserts. The low values in the vegetated regions can be explained by the limited soil moisture retrieval capabilities over dense vegetation covers. Soil emission is attenuated by the canopy and tends to saturate the microwave signal with increasing vegetation density, resulting in a decreased sensor sensitivity to soil moisture variations. It is expected that the new low frequency satellite mission (SMOS) will obtain soil moisture products with a higher quality in these regions. The low correlations in the desert regions are likely due to volume scattering or to the dielectric dynamics within the soil. The volume scattering in dry soils causes a higher backscatter under very dry conditions than under conditions when the sub-surface soil layers are somewhat wet. In addition, at low moisture levels the dielectric constant has a reduced sensitivity in response to changes in the soil moisture content. At a global scale the spatial correspondence of both products is high and both products clearly distinguish similar regions with high seasonal and inter annual variations. Based on the global analyses we concluded that the quality of both products was comparable and in the sparse to moderate vegetated regions both products may be beneficial for large scale validation of SMOS soil moisture. Some limitations of the studied products are different, pointing to significant potential for combining both products into one superior soil moisture data set. © The Author(s) 2008