In mouse tooth development, the roots of the first lower molar develop after crown formation to form 2 cylindrical roots by post-natal day 5. This study compared the morphogenesis and cellular events ...of the mesial-root-forming (MRF) and bifurcation-forming (BF) regions, located in the mesial and center of the first lower molar, to better define the developmental mechanisms involved in multi-rooted tooth formation. We found that the mesenchyme in the MRF showed relatively higher proliferation than the bifurcation region. This suggested that spatially regulated mesenchymal proliferation is required for creating cylindrical root structure. The mechanism may involve the mesenchyme forming a physical barrier to epithelial invagination of Hertwig’s epithelial root sheath. To test these ideas, we cultured roots in the presence of pharmacological inhibitors of microtubule and actin polymerization, nocodazole and cytochalasin-D. Cytochalasin D also inhibits proliferation in epithelium and mesenchyme. Both drugs resulted in altered morphological changes in the tooth root structures. In particular, the nocodazole- and cytochalasin-D-treated specimens showed a loss of root diameter and formation of a single-root, respectively. Immunolocalization and three-dimensional reconstruction results confirmed these mesenchymal cellular events, with higher proliferation in MRF in multi-rooted tooth formation.
Histone methyltransferases (HMTases), as chromatin modifiers, regulate the transcriptomic landscape in normal development as well in diseases such as cancer. Here, we molecularly order two HMTases, ...EZH2 and MMSET, that have established genetic links to oncogenesis. EZH2, which mediates histone H3K27 trimethylation and is associated with gene silencing, was shown to be coordinately expressed and function upstream of MMSET, which mediates H3K36 dimethylation and is associated with active transcription. We found that the EZH2-MMSET HMTase axis is coordinated by a microRNA network and that the oncogenic functions of EZH2 require MMSET activity. Together, these results suggest that the EZH2-MMSET HMTase axis coordinately functions as a master regulator of transcriptional repression, activation, and oncogenesis and may represent an attractive therapeutic target in cancer.
► Coordinated regulation of EZH2 and MMSET in cancer progression ► EZH2 regulates MMSET and its H3K36me2 mark through microRNAs ► MMSET is a downstream mediator of EZH2 oncogenic function ► MMSET overexpression promotes diverse oncogenic phenotypes in vitro and in vivo
Objective
Sinonasal squamous cell carcinoma (SCC) is rare with no consensus on treatment regimen. Our goal is to analyze treatment outcomes in poorly differentiated SCC (PDSCC) using a large national ...database.
Study Design
Retrospective database study.
Methods
The National Cancer Database was queried for sinonasal invasive SCC, grade 3 (poorly differentiated) from 2004 to 2014. Patient demographics and tumor and treatment characteristics were tabulated. Kaplan–Meier (KM) analysis was performed to compare overall survival (OS) between histology subtype and primary site. Multivariable Cox proportional hazards regression was performed for statistical analysis of treatment regimen on OS.
Results
A total of 1,074 patients were identified. The maxillary sinus was the most common site (45%). T4 tumors were observed in 50% of patients, with most patients treated at high‐volume facilities (77%). In KM analysis, spindle cell SCC histological subtype, primary tumors of the maxillary sinus, and poorly differentiated grade had worse OS. In our Cox‐PH model, higher T stage and age were associated with worse OS. Those treated at a high‐volume facility and those who underwent surgical resection followed by adjuvant radiation had improved OS. Chemotherapy within the treatment regimen did not confer survival benefit except in surgical patients when positive margins were present, and surgery with adjuvant chemoradiation trended toward improved survival.
Conclusions
Sinonasal PDSCC appears to be best treated at high‐volume centers with surgical resection followed by adjuvant radiation. Poorly differentiated grade has worse OS compared to more differentiated tumors. Chemotherapy along with adjuvant radiation may have a role in patients with positive surgical margins.
Level of evidence
4 Laryngoscope, 131:E1040–E1048, 2021
We demonstrate efficient terahertz (THz) modulation by coupling graphene strongly with a broadband THz metasurface device. This THz metasurface, made of periodic gold slit arrays, shows near unity ...broadband transmission, which arises from coherent radiation of the enhanced local-field in the slits. Utilizing graphene as an active load with tunable conductivity, we can significantly modify the local-field enhancement and strongly modulate the THz wave transmission. This hybrid device also provides a new platform for future nonlinear THz spectroscopy study of graphene.
CASCADE3 A Monte Carlo event generator based on TMDs Baranov, S.; Bermudez Martinez, A.; Estevez Banos, L. I. ...
European physical journal. C, Particles and fields,
05/2021, Letnik:
81, Številka:
5
Journal Article
Recenzirano
Odprti dostop
The
Cascade3
Monte Carlo event generator based on Transverse Momentum Dependent (TMD) parton densities is described. Hard processes which are generated in collinear factorization with LO multileg or ...NLO parton level generators are extended by adding transverse momenta to the initial partons according to TMD densities and applying dedicated TMD parton showers and hadronization. Processes with off-shell kinematics within
k
t
-factorization, either internally implemented or from external packages via LHE files, can be processed for parton showering and hadronization. The initial state parton shower is tied to the TMD parton distribution, with all parameters fixed by the TMD distribution.
The purpose of this study was to compare the marginal adaptation of two flowable bulk fill resin-based composites (FB-RBCs), two restorative bulk fill resin-based composites (RB-RBCs), and one ...regular incremental-fill RBC in MOD cavities in vitro. Additionally, the influence of linear polymerization shrinkage, shrinkage force, flexural modulus, and bottom/top surface hardness ratio on the marginal adaptation was evaluated.
A Class II MOD cavity was prepared in 40 extracted sound lower molars. In group 1 (control group), the preparation was filled with Filtek Z350 (Z3, 3M ESPE, St Paul, MN, USA) using the incremental filling technique. The FB-RBCs, SDR (SD, group 2) (Dentsply Caulk, Milford, DE, USA) and Venus Bulk Fill (VB, group 3) (Heraeus Kulzer, Dormagen, Germany), were placed in the core portion of the cavity first, and Z350 was filled in the remaining cavity. The RB-RBCs, Tetric N-Ceram Bulkfill (TB, group 4) (Ivoclar Vivadent, Schaan, Liechtenstein) and SonicFill (SF, Group 5) (Kerr, West Collins, Orange, CA, USA), were bulk filled into the preparation. Images of the magnified marginal area were captured under 100× magnification before and after thermomechanical loading, and the percentage ratio of the imperfect margin (%IM
) was calculated. Gaps, cracks in the enamel layer, and chipping of composite, enamel, or dentin were all considered to be imperfect margins. Linear polymerization shrinkage, polymerization shrinkage force, flexural strength, flexural modulus, and bottom/top surface hardness ratio of were measured. Eight specimens were allocated for each material for each test. One-way analysis of variance with the Scheffé test was used to compare the groups at a 95% confidence level.
Before thermomechanical loading, %IM
was in the order of group 3 ≤ groups 2 and 5 ≤ groups 1 and 4 (p=0.011), whereas after loading, it was in the order of group 4 ≤ group 5 ≤ group 1 ≤ groups 2 and 3 (p<0.001). The order of materials were Z3 < TB and SF < SD and VB (p<0.001) in polymerization shrinkage; SF ≤ TB ≤ Z3 < SD < VB (p<0.001) in polymerization shrinkage force; VB < SD < TB ≤ Z3 ≤ SF (p<0.001) in flexural modulus; SD, VB, and TB < Z3 and SF (p<0.001) in flexural strtength; and SF< Z3 < TB < VB and SD (p<0.001) in bottom/top surface hardness ratio. The Pearson correlation constant between %IM
and polymerization shrinkage, shrinkage force, elastic modulus, and bottom/top surface hardness ratio was 0.697, 0.708, -0.373, and 0.353, respectively, after thermomechanical loading.
Within the limitations of this study, RB-RBCs showed better marginal adaptation than FB- RBCs. The lower level of polymerization shrinkage and polymerization shrinkage stress in RB-RBCs seems to contribute to this finding because it would induce less polymerization shrinkage force at the margin. FB-RBCs with lower flexural modulus may not provide an effective buffer to occlusal stress when they are capped with regular RBCs.
•Kerosene enthalpies were estimated at different temperatures using samples and simulations.•Numerical ORC and financial models were developed to assess feasibility of waste heat-to-power ...conversion.•Six pure fluids and two mixtures were investigated for selecting optimum fluid.•It is technically and economically feasible to install a 250kW ORC unit to capture kerosene waste heat.
Industrial waste heat is a large potential resource for generation of carbon-free electricity. This study investigates the technical and economic feasibility of converting waste heat from a stream of liquid kerosene which must be cooled down to control the vacuum distillation temperature. The process conditions were determined for a simple 250kW organic Rankine cycle (ORC) with a heat extraction loop. The pinch point technique was adopted to determine the optimum evaporation and condensation temperatures and assess the influence of the kerosene temperature at the evaporator exit on net power output. The operating conditions and performance of the ORC system were evaluated with eight potential refrigerants and refrigerant mixtures such as R123, R134a, R245fa, isobutane, butane, pentane, an equimolar mixture of butane and pentane, and a mixture of 40% isobutane and 50% butane on a mole basis. A financial model was established for the total plant cost. Results show that isobutane, of the pure fluids, yields the best plant efficiency of 6.8% with approximately half of the kerosene flow available, and the efficiency can be increased up to 7.6% using the butane/pentane mixture. The optimum kerosene temperature at the evaporator outlet is estimated to be 70°C for all the fluid, except the butane/pentane mixture, which meets the design constraint not to disturb the existing distillation process. A capital cost target of $3000/kW could be achieved with a payback period of 6.8years and the internal rate of return (IRR) of 21.8%. Therefore, if the detailed engineering, component fabrication and construction can be achieved within the cost target, the installation of a 250kW ORC waste heat power converter on the kerosene cooling line would be technically feasible and economically viable.
ABSTRACT
This paper presents a rereading of David Little and Sumner Twiss's Comparative Religious Ethics in the context of its initial reception and legacy within the field of religious ethics and ...argues that we can read it more charitably as a piece of pragmatism rather than as a work of formalism or semi‐formalism. If one does not read Little and Twiss as committed positivists concerned with realizing a specific research program associated with the “twilight of logical empiricism,” then their theoretical and methodological recommendations, illustrated in their case studies, appear more pragmatic in nature and less excessively rigid. By rereading Comparative Religious Ethics in this light, we can see more clearly its relevance for the field today, particularly regarding the fundamental importance of the discursive activity of practical reasoning, or the game of giving and asking for reasons, in the study of religious ethics.
B lymphocytes regulate several aspects of immunity including antibody production, cytokine secretion, and T‐cell activation; moreover, B cell misregulation is implicated in autoimmune disorders and ...cancers such as multiple sclerosis and non‐Hodgkin's lymphomas. The delivery of messenger RNA (mRNA) into B cells can be used to modulate and study these biological functions by means of inducing functional protein expression in a dose‐dependent and time‐controlled manner. However, current in vivo mRNA delivery systems fail to transfect B lymphocytes and instead primarily target hepatocytes and dendritic cells. Here, the design, synthesis, and biological evaluation of a lipid nanoparticle (LNP) system that can encapsulate mRNA, navigate to the spleen, transfect B lymphocytes, and induce more than 60 pg of protein expression per million B cells within the spleen is described. Importantly, this LNP induces more than 85% of total protein production in the spleen, despite LNPs being observed transiently in the liver and other organs. These results demonstrate that LNP composition alone can be used to modulate the site of protein induction in vivo, highlighting the critical importance of designing and synthesizing new nanomaterials for nucleic acid delivery.
B‐lymphocytesregulate several aspects of immunity, but B‐cell dysfunction can also serve as the root of disease. Accordingly, it is important to develop chemical tools that can modulate pathways associated with B‐cell function. A new class of ionizable lipid materials is synthesized that, when formulated into messenger RNA lipid nanoparticles, induces protein expression within B‐lymphocytes in mice.
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