Microstructural and Mechanical Properties of Al2O3 and Al2O3/TiB2 Ceramics Consolidated by Plasma Pressure Compaction

Alumina oxide ceramics were produced by plasma pressure compaction (P2C) sintering process. Two types of pure α-alumina (Al2O3) and a mixture of alumina and titanium diboride (TiB2) powders were used as starting materials. Microstructure and mechanical properties, namely hardness, elastic modulus, and fracture toughness, were analyzed and correlated to the type of the sintered powders and the adopted manufacturing route. The microstructural development and the chemical composition variation induced by the sintering process were assessed by using scanning electron microscopy and x-ray diffraction. Nano-indentation and Chevron notch beam techniques were adopted to estimate the mechanical properties of the sintered ceramics. The conducted analyses show the capability of P2C technique to produce sound alumina ceramics. Pure alumina bulks exhibit a good level of compaction and mechanical properties close to those achievable with conventional sintering processes, such as hot isostatic pressing or spark plasma sintering. No significant alterations in the chemical composition of the ceramics were observed. The addition of the titanium diboride in the alumina powders caused a moderate increase in the grain size lowering the hardness and Young’s modulus of the sintered alumina and, at the same time, increased its fracture toughness to the occurrence of toughening mechanisms, like crack bridging and crack deflection

Is Cooled Radiofrequency Genicular Nerve Block and Ablation a Viable Option for the Treatment of Knee Osteoarthritis?

Background The purpose of this study was to determine demographic and psychosocial factors that influence the effectiveness of cooled radiofrequency genicular nerve ablation (C-RFA) and block in patients with chronic knee pain secondary to osteoarthritis (OA). Methods A retrospective review was completed including patients with knee OA who underwent genicular nerve ablation or block or both. Patient information collected included opioid use, psychological comorbidities, smoking history, body mass index, and medical comorbidities. Success was defined using the Osteoarthritis Research Society International criterion of greater than or equal to 50% reported pain relief from the procedure. Patients without a diagnosis of knee OA and patients with ipsilateral total knee arthroplasty were excluded. Patient factors were compared between (1) those that did or did not respond to the initial block and (2) those that did or did not respond to C-RFA. Results Of the 176 subjects that underwent genicular nerve block, 31.8% failed to respond to the procedure. Subjects that failed the initial block were significantly more likely to have psychological comorbidities, smoking history, and diabetes. Of the subjects that proceeded to genicular nerve ablation, 53.7% reported less than 50% pain relief, and 46.3% reported pain relief greater than or equal to 50% at the first follow-up visit. While the presence of psychological comorbidities, smoking, and diabetes were associated with first-stage block failures, these patient factors were not associated with second-stage ablation failures. Conclusions C-RFA may be an effective adjunct therapy as part of a multimodal pain regimen; however, individual patient characteristics must be considered

Asymmetric Organocatalysis and Continuous Chemistry for an Efficient and Cost-Competitive Process to Pregabalin

Herein, we present the scale up development of an innovative synthetic process to pregabalin. The process is underpinned by two enabling technologies critical to its success; continuous chemistry allowed a safe and clean production of nitroalkene, and asymmetric organocatalysis gave access to the chiral intermediate in an enantioenriched form. Crucial to the success of the process was the careful development of a continuous process to nitroalkene and optimization of the organocatalyst and of the reaction conditions to attain remarkably high turn-over frequency in the catalytic asymmetric reaction. Successful recycle of the organocatalysts was also developed in order to achieve a cost-competitive process

Dissociative electron attachment to the H2O molecule. I. Complex-valued potential-energy surfaces for the 2B1, 2A1, and 2B2 metastable states of the water anion

We present the results of calculations defining global, three-dimensional representations of the complex-valued potential-energy surfaces of the doublet B1, doublet A1, and doublet B2 metastable states of the water anion that underlie the physical process of dissociative electron attachment to water. The real part of the resonance energies is obtained from configuration-interaction calculations performed in a restricted Hilbert space, while the imaginary part of the energies (the widths) is derived from complex Kohn scattering calculations. A diabatization is performed on the 2A1 and 2B2 surfaces, due to the presence of a conical intersection between them. We discuss the implications that the shapes of the constructed potential-energy surfaces will have upon the nuclear dynamics of dissociative electron attachment to H2O. This work originally appeared as Phys Rev A 75, 012710 (2007). Typesetting errors in the published version have been corrected here.Comment: Corrected version of PRA 75, 012710 (2007

Maize hybrid X08B746

A novel maize variety designated X08B746 and seed, plants and plant parts thereof, produced by crossing Pioneer Hi Bred International, Inc. proprietary inbred maize varieties. Methods for producing a maize plant that comprises crossing hybrid maize variety X08B746 with another maize plant. Methods for producing a maize plant containing in its genetic material one or more traits introgressed into X08B746 through backcross conversion and/or transformation, and to the maize seed, plant and plant part produced thereby. This invention relates to the maize variety X08B746, the seed, the plant produced from the seed, and variants, mutants, and minor modifications of maize variety X08B746. This inven tion further relates to methods for producing maize varieties derived from maize variety X08B746

β[beta]-Catenin and FGFR2 regulate postnatal rosette-based adrenocortical morphogenesis

Rosettes are widely used in epithelial morphogenesis during embryonic development and organogenesis. However, their role in postnatal development and adult tissue maintenance remains largely unknown. Here, we show zona glomerulosa cells in the adult adrenal cortex organize into rosettes through adherens junction-mediated constriction, and that rosette formation underlies the maturation of adrenal glomerular structure postnatally. Using genetic mouse models, we show loss of beta-catenin results in disrupted adherens junctions, reduced rosette number, and dysmorphic glomeruli, whereas beta-catenin stabilization leads to increased adherens junction abundance, more rosettes, and glomerular expansion. Furthermore, we uncover numerous known regulators of epithelial morphogenesis enriched in beta-catenin-stabilized adrenals. Among these genes, we show Fgfr2 is required for adrenal rosette formation by regulating adherens junction abundance and aggregation. Together, our data provide an example of rosette-mediated postnatal tissue morphogenesis and a framework for studying the role of rosettes in adult zona glomerulosa tissue maintenance and function

Generation of glucocorticoid-producing cells derived from human pluripotent stem cells

Adrenal insufficiency is a life-threatening condition resulting from the inability to produce adrenal hormones in a dose- and time-dependent manner. Establishing a cell-based therapy would provide a physiologically responsive approach for the treatment of this condition. We report the generation of large numbers of human-induced steroidogenic cells (hiSCs) from human pluripotent stem cells (hPSCs). Directed differentiation of hPSCs into hiSCs recapitulates the initial stages of human adrenal development. Following expression of steroidogenic factor 1, activation of protein kinase A signaling drives a steroidogenic gene expression profile most comparable to human fetal adrenal cells, and leads to dynamic secretion of steroid hormones, in vitro. Moreover, expression of the adrenocorticotrophic hormone (ACTH) receptor/co-receptor (MC2R/MRAP) results in dose-dependent ACTH responsiveness. This protocol recapitulates adrenal insufficiency resulting from loss-of-function mutations in AAAS, which cause the enigmatic triple A syndrome. Our differentiation protocol generates sufficient numbers of hiSCs for cell-based therapy and offers a platform to study disorders causing adrenal insufficiency

Generation of glucocorticoid-producing cells derived from human pluripotent stem cells.

Adrenal insufficiency is a life-threatening condition resulting from the inability to produce adrenal hormones in a dose- and time-dependent manner. Establishing a cell-based therapy would provide a physiologically responsive approach for the treatment of this condition. We report the generation of large numbers of human-induced steroidogenic cells (hiSCs) from human pluripotent stem cells (hPSCs). Directed differentiation of hPSCs into hiSCs recapitulates the initial stages of human adrenal development. Following expression of steroidogenic factor 1, activation of protein kinase A signaling drives a steroidogenic gene expression profile most comparable to human fetal adrenal cells, and leads to dynamic secretion of steroid hormones, in vitro. Moreover, expression of the adrenocorticotrophic hormone (ACTH) receptor/co-receptor (MC2R/MRAP) results in dose-dependent ACTH responsiveness. This protocol recapitulates adrenal insufficiency resulting from loss-of-function mutations in AAAS, which cause the enigmatic triple A syndrome. Our differentiation protocol generates sufficient numbers of hiSCs for cell-based therapy and offers a platform to study disorders causing adrenal insufficiency