3,003 research outputs found
Deformations of coisotropic submanifolds for fibrewise entire Poisson structures
We show that deformations of a coisotropic submanifold inside a fibrewise
entire Poisson manifold are controlled by the -algebra introduced by
Oh-Park (for symplectic manifolds) and Cattaneo-Felder. In the symplectic case,
we recover results previously obtained by Oh-Park. Moreover we consider the
extended deformation problem and prove its obstructedness
Deformations of symplectic foliations
We develop the deformation theory of symplectic foliations, i.e. regular foliations equipped with a leafwise symplectic form. The main result of this paper is that each symplectic foliation has an attached -algebra controlling its deformation problem. Indeed, viewing symplectic foliations as regular Poisson structures, we establish a one-to-one correspondence between the small deformations of a given symplectic foliation and the Maurer-Cartan elements of the associated -algebra. Using this, we show that infinitesimal deformations of symplectic foliations can be obstructed. Further, we relate symplectic foliations with foliations on one side and with (arbitrary) Poisson structures on the other, showing that obstructed infinitesimal deformations of the former may give rise to unobstructed infinitesimal deformations of the latter
Structure of the space of folding protein sequences defined by large language models
Proteins populate a manifold in the high-dimensional sequence space whose
geometrical structure guides their natural evolution. Leveraging
recently-developed structure prediction tools based on transformer models, we
first examine the protein sequence landscape as defined by the folding score
function. This landscape shares characteristics with optimization challenges
encountered in machine learning and constraint satisfaction problems. Our
analysis reveals that natural proteins predominantly reside in wide, flat
minima within this energy landscape. To investigate further, we employ
statistical mechanics algorithms specifically designed to explore regions with
high local entropy in relatively flat landscapes. Our findings indicate that
these specialized algorithms can identify valleys with higher entropy compared
to those found using traditional methods such as Monte Carlo Markov Chains. In
a proof-of-concept case, we find that these highly entropic minima exhibit
significant similarities to natural sequences, especially in critical key sites
and local entropy. Additionally, evaluations through Molecular Dynamics
suggests that the stability of these sequences closely resembles that of
natural proteins. Our tool combines advancements in machine learning and
statistical physics, providing new insights into the exploration of sequence
landscapes where wide, flat minima coexist alongside a majority of narrower
minima
Urgent challenges in implementing live attenuated influenza vaccine.
Conflicting reports have emerged about the effectiveness of the live attenuated influenza vaccine. The live attenuated influenza vaccine appears to protect particularly poorly against currently circulating H1N1 viruses that are derived from the 2009 pandemic H1N1 viruses. During the 2015-16 influenza season, when pandemic H1N1 was the predominant virus, studies from the USA reported a complete lack of effectiveness of the live vaccine in children. This finding led to a crucial decision in the USA to recommend that the live vaccine not be used in 2016-17 and to switch to the inactivated influenza vaccine. Other countries, including the UK, Canada, and Finland, however, have continued to recommend the use of the live vaccine. This policy divergence and uncertainty has far reaching implications for the entire global community, given the importance of the production capabilities of the live attenuated influenza vaccine for pandemic preparedness. In this Personal View, we discuss possible explanations for the observed reduced effectiveness of the live attenuated influenza vaccine and highlight the underpinning scientific questions. Further research to understand the reasons for these observations is essential to enable informed public health policy and commercial decisions about vaccine production and development in coming years
A novel protocol for the one-pot borylation/Suzuki reaction provides easy access to hinge-binding groups for kinase inhibitors
The one-pot borylation/Suzuki reaction is a very efficient means of accessing cross-coupling products of two aryl-halide partners that generally requires the use of specific catalysts or ligands and/or relatively long reaction times. This new microwave-assisted method provides a quick one-pot borylation/Suzuki reaction protocol that we applied to the synthesis of various bi- or poly-aryl scaffolds, including a variety of aryl and heteroaryl ring systems and the core frameworks of kinase inhibitors vemurafenib and GDC-0879
Pancreatic cancer-derived S-100A8 N-terminal peptide: a diabetes cause?
BACKGROUND:
Our aim was to identify the pancreatic cancer diabetogenic peptide.
METHODS:
Pancreatic tumor samples from patients with (n=15) or without (n=7) diabetes were compared with 6 non-neoplastic pancreas samples using SDS-PAGE.
RESULTS:
A band measuring approximately 1500 Da was detected in tumors from diabetics, but not in neoplastic samples from non-diabetics or samples from non-neoplastic subjects. Sequence analysis revealed a 14 amino acid peptide (1589.88 Da), corresponding to the N-terminal of the S100A8. At 50 nmol/L and 2 mmol/L, this peptide significantly reduced glucose consumption and lactate production by cultured C(2)C(12) myoblasts. The 14 amino acid peptide caused a lack of myotubular differentiation, the presence of polynucleated cells and caspase-3 activation.
CONCLUSIONS:
The 14 amino acid peptide from S100A8 impairs the catabolism of glucose by myoblasts in vitro and may cause hyperglycemia in vivo. Its identification in biological fluids might be helpful in diagnosing pancreatic cancer in patients with recent onset diabetes mellitus
The (Evolving) vineyard\u2019s age structure in the valencian community, Spain. A new demographic approach for rural development and landscape analysis
Vineyards have assumed a key role as rural landmarks in recent decades. Investigating vineyard dynamics and contexts may reveal various economic, cultural, and environmental aspects of rural landscapes, which can be linked to land-use changes and major soil degradation processes, including soil erosion. As a contribution to rural landscape studies, the purpose of this work is to investigate the spatial distribution of vineyard plots in the Valencian community, located in the eastern area of the Iberian Peninsula, focusing on the final product, the type of vineyard and how long each vineyard has been settled over time. The work provides a comprehensive analysis of a wine-growing landscape, considering strategic (spatial) assets in present and past times. Vineyards were interpreted as a distinctive landmarks that give value to local economies, basic knowledge of how long different types of wine plots have been present in the Valencian community is useful when estimating their degree of sustainability and formulating suggestions, policies, and strategies to prevent processes of landscape degradation at various spatial scales
CONCETTI GIURIDICI E SEMANTICA COGNITIVA
La presente tesi di dottorato esamina criticamente l'applicabilit\ue0 della semantica cognitiva allo studio dei concetti giuridici, in particolare attraverso l'analisi del caso paradigmatico costituito dal concetto di propriet\ue0.This Ph.D. thesis examines critically the possibility of applying cognitive semantics to legal concepts, especially through the analysis of a paradigmatic case, i.e., the concept of property
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