365 research outputs found
Spatial configuration shapes student social and informal learning activities in educational complexes
Notable gains have been made in understanding the factors that influence student experiences
in higher education, particularly in the area of spatial configuration. Indeed, studies have found
that spatial configuration affects spatial behaviour and movement patterns (e.g., Hillier et
al., 1993). Increasingly physical and spatial supports are provided to ensure the efficacy and
efficiency of learning activities in higher education (Higgins et al., 2005; Brown & Long, 2006;
Dugdale & Long, 2007; Dugdale, 2009). Consequently, the informal learning spaces became
a pivotal architectural design strategy for universities to enhance interior design quality and
improve learning environments. It is definitely an effective way to improve learning performance
in the higher educational facilities if well-designed informal learning spaces could improve
student experiences within them. Even though the development of purpose-built informal
learning spaces is a strategy to enhance student experiences, it is becoming more prevalent.
The empirical research in this area is still lacking. What appears to be missing in this enquiry is
how the built environment, namely the shape of the learning environment, influences student
activities.
Using Hillier’s (2007) definition of intelligibility as the relationship between local and global
configurational factors, this paper aims to examine the impact of spatial configuration upon
frequency of student activities in an educational complex based on space syntax theory and
behavioural observation. In order to achieve this assumption, we correlated the data between
the observation data of the frequencies of six student activities: Focused Informal Learning,
Serendipitous Encounter, Intermittent Exchange, Focused Socialising, Dietary Related
Activities and Ambient Sociality. The spatial attributes were derived from space syntax theory in
an educational complex of the University Park campus in the University of Nottingham: Coates
Building - Pope Building - ESLC area. More specifically, there are five informal learning spaces
in the educational complex in total. The frequency of the six types of student activities were examined in five informal learning spaces in this educational complex. The findings confirm that
spatial configuration and patterns of spatial usage are related to each other. The main finding
is that there is a correlation between the degree of connectivity of the area and frequency of
student activities. The finding suggests that spatial configuration may play an important role in
determining frequencies of students socialising and informal learning activities
vandetanib improves anti tumor effects of l19mtnfα in xenograft models of esophageal cancer
Purpose: Targeting the tumor vasculature by vascular disrupting agents (VDAs) has shown therapeutic activity in mouse models. In most cases, however, VDA efficacy is substantially compromised by the inability of these drugs to completely kill tumor cells located at the periphery of the tumor mass. In this study, we investigated anti-tumor effects of L19mTNFα, a fusion protein composed of L19 (scFv), specific for the angiogenesis-associated ED-B containing fibronectin isoform, and murine TNFα, in xenograft models of esophageal cancer. Experimental design: We evaluated ED-B expression in esophageal cancer samples. Subsequently, we generated subcutaneous xenografts from primary tumors, treated them with the L19mTNFα scFv, and determined effects on tumor vasculature, viability and proliferation, and VEGF expression and infiltration by hematopoietic cells. To overcome tumor resistance, L19mTNFα scFv was combined with vandetanib, a tyrosine kinase inhibitor of VEGF receptor, epidermal growth factor receptor, and RET signaling. Results: ED-B was broadly expressed by esophageal cancer cell lines, as well as xenografts and primary surgical samples of esophageal cancer. Administration of L19mTNFα acutely damaged tumor vasculature and increased necrosis, indicating a VDA-like activity of this immunoconjugate. This event was followed, however, by rapid tumor growth recovery associated with increased expression of VEGF and recruitment of CD11b+Gr1+ myeloid cells into tumors. Combination of L19mTNFα with vandetanib severely impaired vascular functions in tumors, leading to a reduction of cell proliferation and increased necrosis, without apparent signs of toxicity. Conclusion: These findings indicate that a combination of vascular damaging agents with anti-angiogenic drugs could represent a promising therapeutic strategy for esophageal cancer. Clin Cancer Res; 17(3); 447–58. ©2010 AACR
BoBafit: A copy number clustering tool designed to refit and recalibrate the baseline region of tumors’ profiles
Human cancer arises from a population of cells that have acquired a wide range of genetic alterations, most of which are targets of therapeutic treatments or are used as prognostic factors for patient's risk stratification. Among these, copy number alterations (CNAs) are quite frequent. Currently, several molecular biology technologies, such as microarrays, NGS and single-cell approaches are used to define the genomic profile of tumor samples. Output data need to be analyzed with bioinformatic approaches and particularly by employing computational algorithms. Molecular biology tools estimate the baseline region by comparing either the mean probe signals, or the number of reads to the reference genome. However, when tumors display complex karyotypes, this type of approach could fail the baseline region estimation and consequently cause errors in the CNAs call. To overcome this issue, we designed an R-package, BoBafit, able to check and, eventually, to adjust the baseline region, according to both the tumor-specific alterations’ context and the sample-specific clustered genomic lesions. Several databases have been chosen to set up and validate the designed package, thus demonstrating the potential of BoBafit to adjust copy number (CN) data from different tumors and analysis techniques. Relevantly, the analysis highlighted that up to 25% of samples need a baseline region adjustment and a redefinition of CNAs calls, thus causing a change in the prognostic risk classification of the patients. We support the implementation of BoBafit within CN analysis bioinformatics pipelines to ensure a correct patient's stratification in risk categories, regardless of the tumor type
The good, the bad and the twisted: a survey of ligand geometry in protein crystal structures
The protein databank now contains the structures of over 11,000 ligands bound to proteins. These structures are invaluable in applied areas such as structure-based drug design, but are also the substrate for understanding the energetics of intermolecular interactions with proteins. Despite their obvious importance, the careful analysis of ligands bound to protein structures lags behind the analysis of the protein structures themselves. We present an analysis of the geometry of ligands bound to proteins and highlight the role of small molecule crystal structures in enabling molecular modellers to critically evaluate a ligand model’s quality and investigate protein-induced strain
Joining participatory approach and spatially-based modelling tools for groundwater resource management.
Although a lot of science has been produced on Water Resource Management (WRM) in the Information and
Communication Technology (ICT) sector, WRM is still poorly addressed via scientific means. Some reasons for
this may be: the underrated importance given to this topic at political and decision-making level; the low-capacity
of the research environment to transfer results; and missing numerical modelling capacities at agencies and
governing authorities.
ICT may provide tools for water planning and management, as discussed within the ICT4WATER cluster initiative.
Among these, GIS-integrated numerical modeling is a robust method to represent hydrological systems and to
provide answers to problems of protection of groundwater resources. Because these tools require a high level
of knowledge pertaining to various disciplines, they are often disregarded as complex “tricky games” providing
unrealistic results. This is a barrier to the uptake of technologies for water management.
To overcome this issue, the application of ICT tools has been combined with an innovative participatory approach,
and large capacity building activities, in the framework of the H2020 FREEWAT project (FREE and open source
software tools for WATer resource management; www.freewat.eu). The major result of the project consists in an
open source and public domain, QGIS-integrated modeling platform for promoting WRM.
FREEWAT capabilities have been demonstrated at 14 case studies in EU and non-EU Countries, where the
effectiveness of few measures foreseen in River Basin Management Plans for achieving good status of water
bodies was tested.
At each case study, a Focus Group (FG) participated by local stakeholders (e.g., river basin authorities, research
institutions, environmental protection agencies, environmental associations) was formed and seven meetings were
organized. During these meetings, the objective of each case study, the methodology to be adopted, including
definition of the conceptual model and of data needed, were discussed. The FG also took decisions on scenarios
to be simulated for testing the feasibility of the foreseen measures. FGs aimed at demonstrating that WRM may
be performed with open source and public domain software and participants’ perception on using ICT tools for
WRM was discussed.
Some of the implemented models are now being used for operational purposes: Vrbansky plato (Slovenia),
where FREEWAT is used to monitor remediation of heating oil spillage and the water supply company intends to
maintain and use developed groundwater flow model for managed groundwater recharge with induced riverbank
filtration; the Bremerhaven case study (Germany), where the local water authority intends to use the developed
groundwater flow model for predictions; the Scarlino-Follonica case study (Italy), where the model will be used by
the regional authority to manage private groundwater remediation projects in a large industrial contaminated site;
the Gozo case study (Malta), where the model is being developed to support the assessment of good groundwater
quantitative status as part of the implementation of the Water Framework Directive
Identification of a Maturation Plasma Cell Index through a Highly Sensitive Droplet Digital PCR Assay Gene Expression Signature Validation in Newly Diagnosed Multiple Myeloma Patients
DNA microarrays and RNA-based sequencing approaches are considered important discovery tools in clinical medicine. However, cross-platform reproducibility studies undertaken so far have highlighted that microarrays are not able to accurately measure gene expression, particularly when they are expressed at low levels. Here, we consider the employment of a digital PCR assay (ddPCR) to validate a gene signature previously identified by gene expression profile. This signature included ten Hedgehog (HH) pathways' genes able to stratify multiple myeloma (MM) patients according to their self-renewal status. Results show that the designed assay is able to validate gene expression data, both in a retrospective as well as in a prospective cohort. In addition, the plasma cells' differentiation status determined by ddPCR was further confirmed by other techniques, such as flow cytometry, allowing the identification of patients with immature plasma cells' phenotype (i.e., expressing CD19+/CD81+ markers) upregulating HH genes, as compared to others, whose plasma cells lose the expression of these markers and were more differentiated. To our knowledge, this is the first technical report of gene expression data validation by ddPCR instead of classical qPCR. This approach permitted the identification of a Maturation Index through the integration of molecular and phenotypic data, able to possibly define upfront the differentiation status of MM patients that would be clinically relevant in the future
Long-term follow-up of patients with relapsing multiple sclerosis from the CLARITY/CLARITY Extension cohort of CLASSIC-MS : an ambispective study
Background: CLASSIC-MS evaluated the long-term efficacy of cladribine tablets in patients with relapsing multiple sclerosis. Objective: Report long-term mobility and disability beyond treatment courses received in CLARITY/CLARITY Extension. Methods: This analysis represents CLASSIC-MS patients who participated in CLARITY with/without participation in CLARITY Extension, and received ⩾1 course of cladribine tablets or placebo (N = 435). Primary objective includes evaluation of long-term mobility (no wheelchair use in the 3 months prior to first visit in CLASSIC-MS and not bedridden at any time since last parent study dose (LPSD), i.e. Expanded Disability Status Scale (EDSS) score <7). Secondary objective includes long-term disability status (no use of an ambulatory device (EDSS < 6) at any time since LPSD). Results: At CLASSIC-MS baseline, mean ± standard deviation EDSS score was 3.9 ± 2.1 and the median time since LPSD was 10.9 (range = 9.3-14.9) years. Cladribine tablets-exposed population: 90.6% (N = 394), including 160 patients who received a cumulative dose of 3.5 mg/kg over 2 years. Patients not using a wheelchair and not bedridden: exposed, 90.0%; unexposed, 77.8%. Patients with no use of an ambulatory device: exposed, 81.2%; unexposed, 75.6%. Conclusion: With a median 10.9 years' follow-up after CLARITY/CLARITY Extension, findings suggest the sustained long-term mobility and disability benefits of cladribine tablets
Blood coagulation dynamics: mathematical modeling and stability results
The hemostatic system is a highly complex multicomponent biosystem that under normal physiologic conditions maintains the fluidity of blood. Coagulation is initiated in response to endothelial surface vascular injury or certain biochemical stimuli, by the exposure of plasma to Tissue Factor (TF), that activates platelets and the coagulation cascade, inducing clot formation, growth and lysis. In recent years considerable advances have contributed to understand this highly complex process and some mathematical and numerical models have been developed. However, mathematical models that are both rigorous and comprehensive in terms of meaningful experimental data, are not available yet. In this paper a mathematical model of coagulation and fibrinolysis in flowing blood that integrates biochemical, physiologic and rheological factors, is revisited. Three-dimensional numerical simulations are performed in an idealized stenosed blood vessel where clot formation and growth are initialized through appropriate boundary conditions on a prescribed region of the vessel wall. Stability results are obtained for a simplified version of the clot model in quiescent plasma, involving some of the most relevant enzymatic reactions that follow Michaelis-Menten kinetics, and having a continuum of equilibria.CEMAT/IST through FCT [PTDC/MAT/68166/2006]; Czech Science Foundation [201/09/0917]; Grant Agency of the Academy of Sciences of the CR [IAA100190804]; Ministry of Education of Czech Republic [6840770010]info:eu-repo/semantics/publishedVersio
A chemically modified antibody mediates complete eradication of tumours by selective disruption of tumour blood vessels
These results reinforce the concept that vascular shutdown can induce a curative avalanche of tumour cell death. Immuno-photodynamic therapy may be particularly indicated for squamous cell carcinoma of the skin, which we show to be strongly positive for markers of angiogenesis
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