Is the List of Incomplete Open Cubes Complete?

Variations of Incomplete Open Cubes is the major project by the twentieth-century conceptual artist Sol LeWitt. In this paper we interpret the enumerative component of the project as embeddings of graphs. This formulation permits use of an algorithm to check the completeness of the list of the structures produced by the artist. Our conclusion is that the artist found the correct number of structures (that is, 122), but that his list contains a mistake in the presentation of a pair of incomplete cubes, a discovery that appears not to have been noted before.     

Thermal stability in bulk cryomilled ultrafine-grained 5083 Al alloy

Thermal stability in bulk ultrafine-grained (UFG) 5083 Al that was processed by gas atomization followed by cryomilling, consolidation, and extrusion, and that exhibited an average grain size of 305 nm, was investigated in the temperature range of 473 to 673 K (0.55 to 0.79 T _m , where T _m is the melting temperature of the material) for different annealing times. Appreciable grain growth was observed at temperatures > 573 K, whereas there was limited grain growth at temperatures < 573 K even after long annealing times. The values of the grain growth exponent, n, deduced from the grain growth data were higher than the value of 2 predicted from elementary grain growth theories. The discrepancy was attributed to the operation of strong pinning forces on boundaries during the annealing treatment. An examination of the microstructure of the alloy suggests that the origin of the pinning forces is most likely related to the presence of dispersion particles, which are mostly introduced during cryomilling. Two-grain growth regimes were identified: the low-temperature region (<573 K) and the high-temperature region (>573 K). For temperatures lower than 573 K, the activation energy of 25 ± 5 kJ/mol was determined. It is suggested that this low activation energy represents the energy for the reordering of grain boundaries in the UFG material. For temperatures higher than 573 K, an activation energy of 124 ± 5 kJ/mol was measured. This value of activation energy, 124 ± 5 kJ/mol, lies between that for grain boundary diffusion and lattice diffusion in analogous aluminum polycrystalline systems. The results show that the strength and ductility of bulk UFG 5083 Al, as obtained from tensile tests, correlate well with substructural changes introduced in the alloy by the annealing treatment.     

An EKV-based high voltage MOSFET model with improved mobility and drift model

An EKV-based high voltage MOSFET model is presented. The intrinsic channel model is derived based on the charge based EKV-formalism. An improved mobility model is used for the modeling of the intrinsic channel to improve the DC characteristics. The model uses second order dependence on the gate bias and an extra parameter for the smoothening of the saturation voltage of the intrinsic drain. An improved drift model [Chauhan YS, Anghel C, Krummenacher F, Ionescu AM, Declercq M, Gillon R, et al. A highly scalable high voltage MOSFET model. In: IEEE European solid-state device research conference (ESSDERC), September 2006. p. 270–3; Chauhan YS, Anghel C, Krummenacher F, Maier C, Gillon R, Bakeroot B, et al. Scalable general high voltage MOSFET model including quasi-saturation and self-heating effect. Solid State Electron 2006;50(11–12):1801–13] is used for the modeling of the drift region, which gives smoother transition on output characteristics and also models well the quasi-saturation region of high voltage MOSFETs. First, the model is validated on the numerical device simulation of the VDMOS transistor and then, on the measured characteristics of the SOI-LDMOS transistor. The accuracy of the model is better than our previous model [Chauhan YS, Anghel C, Krummenacher F, Maier C, Gillon R, Bakeroot B, et al. Scalable general high voltage MOSFET model including quasi-saturation and self-heating effect. Solid State Electron 2006;50(11–12):1801–13] especially in the quasi-saturation region of output characteristics.     

Multitouch tablet applications and activities to enhance the social skills of children with autism spectrum disorders

In spite of great improvements in early diagnosis and interventions, most children diagnosed with autism spectrum disorders (ASD) are unlikely to live independently when they reach adulthood. We have been conducting research on novel computer-based interventions with the goal of promoting social skills. Working with 26 children with ASD, their teachers, and other stakeholders, we have iteratively developed a set of activities based on applications that run on multitouch tablets. Our observations suggest these activities increased pro-social behaviors such as collaboration and coordination, augmented appreciation for social activities, and provided children with novel forms of expression.     

Increased Bone Resorption during Lactation in Pycnodysostosis

Pycnodysostosis, a rare autosomal recessive skeletal dysplasia, is caused by a deficiency of cathepsin K. Patients have impaired bone resorption in the presence of normal or increased numbers of multinucleated, but dysfunctional, osteoclasts. Cathepsin K degrades collagen type I and generates N-telopeptide (NTX) and the C-telopeptide (CTX) that can be quantified. Levels of these telopeptides are increased in lactating women and are associated with increased bone resorption. Nothing is known about the consequences of cathepsin K deficiency in lactating women. Here we present for the first time normalized blood and CTX measurements in a patient with pycnodysostosis, exclusively related to the lactation period. In vitro studies using osteoclasts derived from blood monocytes during lactation and after weaning further show consistent bone resorption before and after lactation. Increased expression of cathepsins L and S in osteoclasts derived from the lactating patient suggests that other proteinases could compensate for the lack of cathepsin K during the lactation period of pycnodysostosis patients.     

Non-Coding RNAs Set a New Phenotypic Frontier in Prostate Cancer Metastasis and Resistance

Prostate cancer (PCa) mortality remains a significant public health problem, as advanced disease has poor survivability due to the development of resistance in response to both standard and novel therapeutic interventions. Therapeutic resistance is a multifaceted problem involving the interplay of a number of biological mechanisms including genetic, signaling, and phenotypic alterations, compounded by the contributions of a tumor microenvironment that supports tumor growth, invasiveness, and metastasis. The androgen receptor (AR) is a primary regulator of prostate cell growth, response and maintenance, and the target of most standard PCa therapies designed to inhibit AR from interacting with androgens, its native ligands. As such, AR remains the main driver of therapeutic response in patients with metastatic castration-resistant prostate cancer (mCRPC). While androgen deprivation therapy (ADT), in combination with microtubule-targeting taxane chemotherapy, offers survival benefits in patients with mCRPC, therapeutic resistance invariably develops, leading to lethal disease. Understanding the mechanisms underlying resistance is critical to improving therapeutic outcomes and also to the development of biomarker signatures of predictive value. The interconversions between epithelial-to-mesenchymal transition (EMT) and mesenchymal-to-epithelial transition (MET) navigate the prostate tumor therapeutic response, and provide a novel targeting platform in overcoming therapeutic resistance. Both microRNA (miRNA)- and long non-coding RNA (lncRNA)-mediated mechanisms have been associated with epigenetic changes in prostate cancer. This review discusses the current evidence-based knowledge of the role of the phenotypic transitions and novel molecular determinants (non-coding RNAs) as contributors to the emergence of therapeutic resistance and metastasis and their integrated predictive value in prostate cancer progression to advanced disease.     

Thrombospondin-1 CD47 Signalling: From Mechanisms to Medicine

Recent advances provide evidence that the cellular signalling pathway comprising the ligand-receptor duo of thrombospondin-1 (TSP1) and CD47 is involved in mediating a range of diseases affecting renal, vascular, and metabolic function, as well as cancer. In several instances, research has barely progressed past pre-clinical animal models of disease and early phase 1 clinical trials, while for cancers, anti-CD47 therapy has emerged from phase 2 clinical trials in humans as a crucial adjuvant therapeutic agent. This has important implications for interventions that seek to capitalize on targeting this pathway in diseases where TSP1 and/or CD47 play a role. Despite substantial progress made in our understanding of this pathway in malignant and cardiovascular disease, knowledge and translational gaps remain regarding the role of this pathway in kidney and metabolic diseases, limiting identification of putative drug targets and development of effective treatments. This review considers recent advances reported in the field of TSP1-CD47 signalling, focusing on several aspects including enzymatic production, receptor function, interacting partners, localization of signalling, matrix-cellular and cell-to-cell cross talk. The potential impact that these newly described mechanisms have on health, with a particular focus on renal and metabolic disease, is also discussed.     

Molecular Genetics of Conjunctival Melanoma and Prognostic Value of TERT Promoter Mutation Analysis

The aim of this study was exploration of the genetic background of conjunctival melanoma (CM) and correlation with recurrent and metastatic disease. Twenty-eight CM from the Rotterdam Ocular Melanoma Study group were collected and DNA was isolated from the formalin-fixed paraffin embedded tissue. Targeted next-generation sequencing was performed using a panel covering GNAQ, GNA11, EIF1AX, BAP1, BRAF, NRAS, c-KIT, PTEN, SF3B1, and TERT genes. Recurrences and metastasis were present in eight (29%) and nine (32%) CM cases, respectively. TERT promoter mutations were most common (54%), but BRAF (46%), NRAS (21%), BAP1 (18%), PTEN (14%), c-KIT (7%), and SF3B1 (4%) mutations were also observed. No mutations in GNAQ, GNA11, and EIF1AX were found. None of the mutations was significantly associated with recurrent disease. Presence of a TERT promoter mutation was associated with metastatic disease (p-value = 0.008). Based on our molecular findings, CM comprises a separate entity within melanoma, although there are overlapping molecular features with uveal melanoma, such as the presence of BAP1 and SF3B1 mutations. This warrants careful interpretation of molecular data, in the light of clinical findings. About three quarter of CM contain drug-targetable mutations, and TERT promoter mutations are correlated to metastatic disease in CM.     

Methacrylic acid and dodecyl methacrylate (MAc‐DMA) hydrogel for enhanced catalytic activity of lipase of Bacillus coagulans MTCC‐6375

An alkaline thermotolerant bacterial lipase of Bacillus coagulans MTCC‐6375 was purified and immobilized on a methacrylic acid and dodecyl methacrylate (MAc‐DMA) hydrogel. The lipase was optimally bound to the matrix after 20 min of incubation at 55°C and pH 9 under shaking conditions. The matrix‐bound lipase retained approximately 50% of its initial activity at 70–80°C after 3 h of incubation. The immobilized lipase was highly active on medium chain length p‐nitrophenyl acyl ester (C: 8, p‐nitrophenyl caprylate) than other p‐nitrophenyl acyl esters. The presence of Fe³⁺, NH₄⁺, K⁺, and Zn²⁺ ions at 1 mM concentration in the reaction mixture resulted in a profound increase in the activity of immobilized lipase. Most of the detergents partially reduced the activity of the immobilized lipase. The immobilized lipase performed ～62% conversion in 12 h at temperature 55°C. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 100: 1420–1426, 2006