This note addresses the issue of energy conservation for the 2D Euler system with an
L
p
-control on vorticity. We provide a direct argument, based on a mollification in physical space, to show that ...the energy of a weak solution is conserved if
ω
=
∇
×
u
∈
L
3
2
. An example of a 2D field in the class
ω
∈
L
3
2
-
ϵ
for any
ε
>
0
, and
u
∈
B
3
,
∞
1
/
3
(Onsager critical space, see Shvydkoy in Discr Contin Dyn Syst Ser S 3(3):473–496,
2010
) is constructed with non-vanishing energy flux. This demonstrates sharpness of the kinematic argument, which does not differentiate between 2D and 3D, and requires Onsager’s regularity control on the solution. Next, we show that for physically realizable solutions there is a mechanism preventing the anomalous dissipation in 2D that does not require such a control. Namely, we prove that any solution to the Euler equations produced via a vanishing viscosity limit from the Navier–Stokes equations, with
ω
∈
L
p
, for
p
> 1, conserves energy.
Amyloidoses are diseases characterized by abnormal protein folding and self-assembly, for which no cure is available. Inhibition or modulation of abnormal protein self-assembly, therefore, is an ...attractive strategy for prevention and treatment of amyloidoses. We examined Lys-specific molecular tweezers and discovered a lead compound termed CLR01, which is capable of inhibiting the aggregation and toxicity of multiple amyloidogenic proteins by binding to Lys residues and disrupting hydrophobic and electrostatic interactions important for nucleation, oligomerization, and fibril elongation. Importantly, CLR01 shows no toxicity at concentrations substantially higher than those needed for inhibition. We used amyloid β-protein (Aβ) to further explore the binding site(s) of CLR01 and the impact of its binding on the assembly process. Mass spectrometry and solution-state NMR demonstrated binding of CLR01 to the Lys residues in Aβ at the earliest stages of assembly. The resulting complexes were indistinguishable in size and morphology from Aβ oligomers but were nontoxic and were not recognized by the oligomer-specific antibody A11. Thus, CLR01 binds already at the monomer stage and modulates the assembly reaction into formation of nontoxic structures. The data suggest that molecular tweezers are unique, process-specific inhibitors of aberrant protein aggregation and toxicity, which hold promise for developing disease-modifying therapy for amyloidoses.
Chromosomal rearrangements of the human MLL/KMT2A gene are associated with infant, pediatric, adult and therapy-induced acute leukemias. Here we present the data obtained from 2345 acute leukemia ...patients. Genomic breakpoints within the MLL gene and the involved translocation partner genes (TPGs) were determined and 11 novel TPGs were identified. Thus, a total of 135 different MLL rearrangements have been identified so far, of which 94 TPGs are now characterized at the molecular level. In all, 35 out of these 94 TPGs occur recurrently, but only 9 specific gene fusions account for more than 90% of all illegitimate recombinations of the MLL gene. We observed an age-dependent breakpoint shift with breakpoints localizing within MLL intron 11 associated with acute lymphoblastic leukemia and younger patients, while breakpoints in MLL intron 9 predominate in AML or older patients. The molecular characterization of MLL breakpoints suggests different etiologies in the different age groups and allows the correlation of functional domains of the MLL gene with clinical outcome. This study provides a comprehensive analysis of the MLL recombinome in acute leukemia and demonstrates that the establishment of patient-specific chromosomal fusion sites allows the design of specific PCR primers for minimal residual disease analyses for all patients.
(
)-mutant lower grade gliomas are classified as oligodendrogliomas or diffuse astrocytomas based on 1p/19q-codeletion status. We aimed to test and validate neuroradiologists' performances in ...predicting the codeletion status of
-mutant lower grade gliomas based on simple neuroimaging metrics.
One hundred two
-mutant lower grade gliomas with preoperative MR imaging and known 1p/19q status from The Cancer Genome Atlas composed a training dataset. Two neuroradiologists in consensus analyzed the training dataset for various imaging features: tumor texture, margins, cortical infiltration, T2-FLAIR mismatch, tumor cyst, T2* susceptibility, hydrocephalus, midline shift, maximum dimension, primary lobe, necrosis, enhancement, edema, and gliomatosis. Statistical analysis of the training data produced a multivariate classification model for codeletion prediction based on a subset of MR imaging features and patient age. To validate the classification model, 2 different independent neuroradiologists analyzed a separate cohort of 106 institutional
-mutant lower grade gliomas.
Training dataset analysis produced a 2-step classification algorithm with 86.3% codeletion prediction accuracy, based on the following: 1) the presence of the T2-FLAIR mismatch sign, which was 100% predictive of noncodeleted lower grade gliomas, (
= 21); and 2) a logistic regression model based on texture, patient age, T2* susceptibility, primary lobe, and hydrocephalus. Independent validation of the classification algorithm rendered codeletion prediction accuracies of 81.1% and 79.2% in 2 independent readers. The metrics used in the algorithm were associated with moderate-substantial interreader agreement (κ = 0.56-0.79).
We have validated a classification algorithm based on simple, reproducible neuroimaging metrics and patient age that demonstrates a moderate prediction accuracy of 1p/19q-codeletion status among
-mutant lower grade gliomas.
The major rDNA genes are composed of tandem repeats and are part of the nucleolus organizing regions (NORs). They are highly conserved and therefore useful in understanding the evolutionary patterns ...of chromosomal locations. The evolutionary dynamics of the karyotype may affect the organization of rDNA genes within chromosomes. In this study, we physically mapped 18S rDNA genes in 13 Neotropical ant species from four subfamilies using fluorescence in situ hybridization. Furthermore, a survey of published rDNA cytogenetic data for 50 additional species was performed, which allowed us to detect the evolutionary patterns of these genes in ant chromosomes. Species from the Neotropical, Palearctic, and Australian regions, comprising a total of 63 species from 19 genera within six subfamilies, were analysed. Most of the species (48 out of 63) had rDNA genes restricted to a single chromosome pair in their intrachromosomal regions. The position of rDNA genes within the chromosomes appears to hinder their dispersal throughout the genome, as translocations and ectopic recombination are uncommon in intrachromosomal regions because they can generate meiotic abnormalities. Therefore, rDNA genes restricted to a single chromosome pair seem to be a plesiomorphic feature in ants, while multiple rDNA sites, observed in distinct subfamilies, may have independent origins in different genera.
Single rDNA site should be considered a plesiomorphic trait in ants because multiple rDNA sites were observed in different non‐related lineages that do not share exclusive common ancestry appearing de novo.
A single pair of chromosomes bearing rDNA clusters is more common in the ant genome because of the pericentromeric/interstitial location of these genes on the chromosomes.
In ant species, terminal rDNA clusters are prone to rearrangements and dispersal as seen in Camponotus renggeri, Dinoponera gigantea, and Myrmecia spp. with multiple NORs in entire short arm (including terminal/subterminal regions).
Targeted overexpression of angiotensin-converting enzyme (ACE), an amyloid-β protein degrading enzyme, to brain resident microglia and peripheral myelomonocytes (ACE10 model) substantially diminished ...Alzheimer's-like disease in double-transgenic APPSWE/PS1ΔE9 (AD+) mice. In this study, we explored the impact of selective and transient angiotensin-converting enzyme overexpression on macrophage behaviour and the relative contribution of bone marrow-derived ACE10 macrophages, but not microglia, in attenuating disease progression. To this end, two in vivo approaches were applied in AD+ mice: (i) ACE10/GFP+ bone marrow transplantation with head shielding; and (ii) adoptive transfer of CD115+-ACE10/GFP+ monocytes to the peripheral blood. Extensive in vitro studies were further undertaken to establish the unique ACE10-macrophage phenotype(s) in response to amyloid-β1-42 fibrils and oligomers. The combined in vivo approaches showed that increased cerebral infiltration of ACE10 as compared to wild-type monocytes (∼3-fold increase; P < 0.05) led to reductions in cerebral soluble amyloid-β1-42, vascular and parenchymal amyloid-β deposits, and astrocytosis (31%, 47-80%, and 33%, respectively; P < 0.05-0.0001). ACE10 macrophages surrounded brain and retinal amyloid-β plaques and expressed 3.2-fold higher insulin-like growth factor-1 (P < 0.01) and ∼60% lower tumour necrosis factor-α (P < 0.05). Importantly, blood enrichment with CD115+-ACE10 monocytes in symptomatic AD+ mice resulted in pronounced synaptic and cognitive preservation (P < 0.05-0.001). In vitro analysis of macrophage response to well-defined amyloid-β1-42 conformers (fibrils, prion rod-like structures, and stabilized soluble oligomers) revealed extensive resistance to amyloid-β1-42 species by ACE10 macrophages. They exhibited 2-5-fold increased surface binding to amyloid-β conformers as well as substantially more effective amyloid-β1-42 uptake, at least 8-fold higher than those of wild-type macrophages (P < 0.0001), which were associated with enhanced expression of surface scavenger receptors (i.e. CD36, scavenger receptor class A member 1, triggering receptor expressed on myeloid cells 2, CD163; P < 0.05-0.0001), endosomal processing (P < 0.05-0.0001), and ∼80% increased extracellular degradation of amyloid-β1-42 (P < 0.001). Beneficial ACE10 phenotype was reversed by the angiotensin-converting enzyme inhibitor (lisinopril) and thus was dependent on angiotensin-converting enzyme catalytic activity. Further, ACE10 macrophages presented distinct anti-inflammatory (low inducible nitric oxide synthase and lower tumour necrosis factor-α), pro-healing immune profiles (high insulin-like growth factor-1, elongated cell morphology), even following exposure to Alzheimer's-related amyloid-β1-42 oligomers. Overall, we provide the first evidence for therapeutic roles of angiotensin-converting enzyme-overexpressing macrophages in preserving synapses and cognition, attenuating neuropathology and neuroinflammation, and enhancing resistance to defined pathognomonic amyloid-β forms.
In the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial, apixaban compared with warfarin reduced the risk of stroke, major bleed, and death in ...patients with atrial fibrillation. In this ancillary study, we evaluated clinical consequences of major bleeds, as well as management and treatment effects of warfarin vs. apixaban.
Major International Society on Thrombosis and Haemostasis bleeding was defined as overt bleeding accompanied by a decrease in haemoglobin (Hb) of ≥2 g/dL or transfusion of ≥2 units of packed red cells, occurring at a critical site or resulting in death. Time to event death, ischaemic stroke, or myocardial infarction (MI) was evaluated by Cox regression models. The excess risk associated with bleeding was evaluated by separate time-dependent indicators for intracranial (ICH) and non-intracranial haemorrhage. Major bleeding occurred in 848 individuals (4.7%), of whom 126 (14.9%) died within 30 days. Of 176 patients with an ICH, 76 (43.2%) died, and of the 695 patients with major non-ICH, 64 (9.2%) died within 30 days of the bleeding. The risk of death, ischaemic stroke, or MI was increased roughly 12-fold after a major non-ICH bleeding event within 30 days. Corresponding risk of death following an ICH was markedly increased, with HR 121.5 (95% CI 91.3-161.8) as was stroke or MI with HR 21.95 (95% CI 9.88-48.81), respectively. Among patients with major bleeds, 20.8% received vitamin K and/or related medications (fresh frozen plasma, coagulation factors, factor VIIa) to stop bleeding within 3 days, and 37% received blood transfusion. There was no interaction between apixaban and warfarin and major bleeding on the risk of death, stroke, or MI.
Major bleeding was associated with substantially increased risk of death, ischaemic stroke, or MI, especially following ICH, and this risk was similarly elevated regardless of treatment with apixaban or warfarin. These results underscore the importance of preventing bleeding in anti-coagulated patients. ClinicalTrials.gov Identifier: NCT00412984.
In this article we examine the interaction of incompressible 2D flows with material boundaries. Our focus is the dynamic behavior of the circulation of velocity around boundary components and the ...possible exchange between flow vorticity and boundary circulation in flows with vortex sheet initial data, in the case of bounded domains. Our point of departure is the observation that ideal flows with vortex sheet regularity have well-defined circulation around each connected component of the boundary. In addition, we show that the velocity can be uniquely reconstructed from the vorticity and boundary component circulations, which allows to recast 2D Euler evolution using vorticity and the circulations as dynamic variables. The weak form of this vortex dynamics formulation of the equations is called the weak vorticity formulation. Existence of a weak solution for the 2D Euler equations, in velocity form, is guaranteed by Delort's Theorem, when the initial vorticity is a bounded measure satisfying a sign condition. The main result in this article is the equivalence between the weak velocity and weak vorticity formulations, without sign assumptions. Despite their being equivalent, the qualitative information concerning weak solutions is more apparent from the weak vorticity formulation than from the velocity formulation, and the remainder of the article is devoted to several consequences which can be derived from our main result. First, we consider weak solutions obtained by mollifying initial data and passing to the limit, with the portion of vorticity singular with respect to the Lebesgue measure assumed to be nonnegative. For these solutions we prove a set of inequalities which restrict the possible generation of vorticity by the boundary. Next, we prove that, if the weak solution conserves circulation around the boundary components, then it is a boundary coupled weak solution, a stronger version of the weak vorticity formulation. We prove existence of a weak solution which conserves circulation around the boundary components if the initial vorticity is integrable, i.e. if the singular part vanishes. Finally, we discuss the definition of the net mechanical force which the flow exerts on each material boundary component and its relation with conservation of circulation.
Customized palatal guide and splint for maxillary expansion Claus, Jonathas Daniel Paggi; Hidalgo, Jaime; Almeida, Matheus Spinella ...
International journal of oral and maxillofacial surgery,
12/2023, Letnik:
52, Številka:
12
Journal Article
Recenzirano
Customization in orthognathic surgery allows better precision and a reduced surgical time. In Le Fort I osteotomy surgery, the maxillary segmentation is considered one of the most unstable procedures ...due to transverse instability. Various different types of palatal device have been proposed to address this instability. This note describes a customized bone-borne palatal guide and splint that may help surgeons shorten the surgical time and achieve better three-dimensional repositioning, with more postoperative comfort for the patient and occlusal control for the surgeon.
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