No evidence for reduced Simon cost in elderly bilinguals and bidialectals

We explored whether a bilingual advantage in executive control is associated with differences in cultural and ethnic background associated with the bilinguals’ immigrant status, and whether dialect use in monolinguals can also incur such an advantage. Performance on the Simon task in older non-immigrant (Gaelic-English) and immigrant (Bengali, Gujarati, Hindi, Malay, Punjabi, Urdu-English) bilinguals was compared with three groups of older monolingual English speakers, who were either monodialectal users of the same English variety as the bilinguals or were bidialectal users of a local variety of Scots. Results showed no group differences in overall reaction times as well as in the Simon effect thus providing no evidence that an executive control advantage is related to differences in cultural and ethnic background as was found for immigrant compared to non-immigrant bilinguals, nor that executive control may be improved by use of dialect. We suggest the role of interactional contexts and bilingual literacy as potential explanations for inconsistent findings of a bilingual advantage in executive control

CD33 Alzheimer’s disease locus: Altered monocyte function and amyloid biology

In our functional dissection of the CD33 Alzheimer’s disease susceptibility locus, we find that the rs3865444C risk allele is associated with greater cell surface expression of CD33 in monocytes (t50 = 10.06, pjoint=1.3×10–13) of young and older individuals. It is also associated with (1) diminished internalization of Aβ42) (2) accumulation of neuritic amyloid pathology and fibrillar amyloid on in vivo imaging and (3), increased numbers of activated human microglia

Nový detailní svalově-kosterní AnyBody model ruky

V situaci, kdy není možné řešit svalově-kosterní výzkum týkající se prevence či rehabilitace ruky pomocí experimentů, lze tyto otázky řešit pomocí počítačové techniky s využitím inverzní dynamiky. Do dnešní doby však nebyl vyvinut žádný komplexní model lidského těla. Hlavním cílem této práce tedy bylo vyvinout a validovat detailní model ruky v softwaru AnyBody Modeling System (AMS) s využitím metody torus-ostacle. A dále pak implementovat tento model do celistvého modelu lidského těla.Musculoskeletal research questions regarding the prevention or rehabilitation of the hand can be addressed using inverse dynamics simulations when experiments are not possible. To date, no complete human hand model implemented in a holistic human body model has been fully developed. The aim of this work was to develop, implement, and validate a fully detailed hand model using the AnyBody Modelling System (AMS) (AnyBody, Aalborg, Denmark) using the torus-ostacle method

Finite element modeling of maximum stress in pelvic floor structures during the head expulsion (FINESSE) study

Several studies have assessed birth-related deformations of the levator ani muscle (LAM) and perineum on models that depicted these elements in isolation. The main aim of this study was to develop a complex female pelvic floor computational model using the finite element method to evaluate points and timing of maximum stress at the LAM and perineum in relation to the birth process. A three-dimensional computational model of the female pelvic floor was created and used to simulate vaginal birth based on data from previously described real-life MRI scans. We developed three models: model A (LAM without perineum); model B (perineum without LAM); model C (a combined model with both structures). The maximum stress in the LAM was achieved when the vertex was 9 cm below the ischial spines and measured 37.3 MPa in model A and 88.7 MPa in model C. The maximum stress in the perineum occurred at the time of distension by the suboocipito-frontal diameter and reached 86.7 MPa and 119.6 MPa in models B and C, respectively, while the stress in the posterior fourchette caused by the suboccipito-bregmatic diameter measured 36.9 MPa for model B and 39.8 MPa for model C. Including perineal structures in a computational birth model simulation affects the level of stress at the LAM. The maximum stress at the LAM and perineum seems to occur when the head is lower than previously anticipated

Pembrolizumab plus enfortumab vedotin in urothelial cancer

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Differential Temperature-Dependent Multimeric Assemblies of Replication and Repair Polymerases on DNA Increase Processivity

Differentiation of binding accurate DNA replication polymerases over error prone DNA lesion bypass polymerases is essential for the proper maintenance of the genome. The hyperthermophilic archaeal organism, Sulfolobus solfataricus (Sso), contains both a B-family replication (Dpo1) and a Y-family repair (Dpo4) polymerase and serves as a model system for understanding molecular mechanisms and assemblies for DNA replication and repair protein complexes. Protein crosslinking, isothermal titration calorimetry, and analytical ultracentrifugation have confirmed a previously unrecognized dimeric Dpo4 complex bound to DNA. Binding discrimination between these polymerases on model DNA templates is complicated by the fact that multiple oligomeric species are influenced by concentration and temperature. Temperature dependent fluorescence anisotropy equilibrium binding experiments were used to separate discrete binding events for formation of trimeric Dpo1 and dimeric Dpo4 complexes on DNA. The associated equilibria are found to be temperature dependent, generally leading to improved binding at higher temperatures for both polymerases. At high temperatures, DNA binding by Dpo1 monomer is favored over Dpo4 monomer, but binding of Dpo1 trimer is even more strongly favored over Dpo4 dimer, thus providing thermodynamic selection. Greater processivities of nucleotide incorporation for trimeric Dpo1 and dimeric Dpo4 are also observed at higher temperatures, providing biochemical validation for the influence of tightly bound oligomeric polymerases. These results separate, quantify, and confirm individual and sequential processes leading to formation of oligomeric Dpo1 and Dpo4 assemblies on DNA and provide for a concentration and temperature dependent discrimination of binding undamaged DNA templates at physiological temperatures