A major challenge exists in the preparation of scaffolds for bone regeneration, namely, achieving simultaneously bioactivity, biocompatibility, mechanical performance and simple manufacturing. Here, ...cellulose nanofibrils (CNF) are introduced for the preparation of scaffolds taking advantage of their biocompatibility and ability to form strong 3D porous networks from aqueous suspensions. CNF are made bioactive for bone formation through a simple and scalable strategy that achieves highly interconnected 3D networks. The resultant materials optimally combine morphological and mechanical features and facilitate hydroxyapatite formation while releasing essential ions for in vivo bone repair. The porosity and roughness of the scaffolds favor several cell functions while the ions act in the expression of genes associated with cell differentiation. Ion release is found critical to enhance the production of the bone morphogenetic protein 2 (BMP-2) from cells within the fractured area, thus accelerating the in vivo bone repair. Systemic biocompatibility indicates no negative effects on vital organs such as the liver and kidneys. The results pave the way towards a facile preparation of advanced, high performance CNF-based scaffolds for bone tissue engineering.
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.
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.
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.
The machining process evolution has been accompanied by the improvement of tool performance, being this mainly due to the development of thin coatings, mono and multi-layered, providing the most ...appropriate set of properties for each machining condition. On the other hand, duplex stainless steels have registered a strong increase in demand, which, in many cases, requires the use of machining processes in order to obtain the final shape accurately. Taking into account these two aspects, this paper aims essentially to evaluate the performance of two cutting inserts with PVD and CVD coatings, used in rough milling operations of duplex stainless steel. The cutting parameters and machining conditions were those recommended by the manufacturer and were kept unchanged in all performed tests. The behavior of the PVD- and CVD-coated cutting tools was assessed using three different facets: (a) surface roughness analysis, (b) tool wear evaluation, and (c) the monitoring of vibration levels produced during each test. CVD (TiN/TiCN/Al
2
O
3
)-coated inserts showed very good suitability to be used as tools for roughing milling operations when machining super duplex stainless steels.
A combination of hydrophobic and electrostatic interactions is important in initiating the aberrant self-assembly process that leads to formation of toxic oligomers and aggregates by multiple ...disease-related proteins, including amyloid β-protein (Aβ), whose self-assembly is believed to initiate brain pathogenesis in Alzheimer’s disease. Lys residues play key roles in this process and participate in both types of interaction. They also are the target of our recently reported molecular tweezer inhibitors. To obtain further insight into the role of the two Lys residues in Aβ assembly and toxicity, here we substituted each by Ala in both Aβ40 and Aβ42 and studied the impact of the substitution on Aβ oligomerization, aggregation, and toxicity. Our data show that each substitution has a major impact on Aβ assembly and toxicity, with significant differences depending on peptide length (40 versus 42 amino acids) and the position of the substitution. In particular, Lys16→Ala substitution dramatically reduces Aβ toxicity. The data support the use of compounds targeting Lys residues specifically as inhibitors of Aβ toxicity and suggest that exploring the role of Lys residues in other disease-related amyloidogenic proteins may help understanding the mechanisms of aggregation and toxicity of these proteins.
De‐Deus G, Moreira EJL, Lopes HP, Elias CN. Extended cyclic fatigue life of F2 ProTaper instruments used in reciprocating movement. International Endodontic Journal
Aim To evaluate the cyclic ...fatigue fracture resistance of engine‐driven F2 ProTaper instruments under reciprocating movement.
Methodology A sample of 30 NiTi ProTaper F2 instruments was used. An artificial canal was made from a stainless steel tube, allowing the instruments to rotate freely. During mechanical testing, different movement kinematics and speeds were used, which resulted in three experimental groups (n = 10). The instruments from the first group (G1) were rotated at a nominal speed of 250 rpm until fracture, whilst the instruments from the second group (G2) were rotated at 400 rpm. In the third instrument group (G3), the files were driven under reciprocating movement. The time of fracture for each instrument was measured, and statistical analysis was performed using parametric methods.
Results Reciprocating movement resulted in a significantly longer cyclic fatigue life (P < 0.05). Moreover, operating rpm was a significant factor affecting cyclic fatigue life (P < 0.05); instruments used at a rotational speed of 400 rpm (approximately 95 s) failed more rapidly than those used at 250 rpm (approximately 25 s).
Conclusions Movement kinematics is amongst the factors determining the resistance of rotary NiTi instruments to cyclic fracture. Moreover, the reciprocating movement promoted an extended cyclic fatigue life of the F2 ProTaper instrument in comparison with conventional rotation.
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