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.     

Electrical coupling and impulse propagation in anatomically modeledventricular tissue

Computer simulations were used to study the role of resistive couplings on flat-wave action potential propagation through a thin sheet of ventricular tissue. Unlike simulations using continuous or periodic structures, this unique electrical model includes random size cells with random spaced longitudinal and lateral connections to simulate the physiologic structure of the tissue. The resolution of the electrical model is ten microns, thus providing a simulated view at the subcellular level. Flat-wave longitudinal propagation was evaluated with an electrical circuit of over 140,000 circuit elements, modeling a 0.25 mm by 5.0 mm sheet of tissue. An electrical circuit of over 84,000 circuit elements, modeling a 0.5 mm by 1.5 mm sheet was used to study flat-wave transverse propagation. Under normal cellular coupling conditions, at the macrostructure level, electrical conduction through the simulated sheets appeared continuous and directional differences in conduction velocity, action potential amplitude and V˙_max were observed. However, at the subcellular level (10 μm) unequal action potential delays were measured at the longitudinal and lateral gap junctions and irregular wave-shapes were observed in the propagating signal. Furthermore, when the modeled tissue was homogeneously uncoupled at the gap junctions conduction velocities decreased as the action potential delay between modeled cells increased. The variability in the measured action potential was most significant in areas with fewer lateral gap junctions, i.e., lateral gap junctions between fibers were separated by a distance of 100 μm or more     

All-trans beta-carotene is absorbed preferentially to 9-cis beta-carotene, but the latter accumulates in the tissues of domestic ferrets (Mustela putorius puro)

The algae Dunaliella bardawil and Dunaliella salina naturally contain large concentrations of all-trans and 9-cis beta-carotene (betaC). The purpose of this study was to compare the relative serum and tissue accumulation of all-trans and 9-cis betaC in ferrets fed different ratios of all-trans/9-cis betaC derived from two commercial sources, D. bardawil or D. salina (Betatene). Male ferrets (7 wk old) were fed carotene-free, pelleted diets for 27 d. Beginning on d 18, groups of ferrets (n = 6 or 7) received daily, one of six oral supplements varying in ratios of 9-cis and all-trans betaC mixed with approximately 1.0mL of Ensure. Four supplements containing 5.2-8.3 micromol total betaC were prepared from a 20% Betatene preparation, D. bardawil, a high-cis Betatene preparation, and Betatene further enriched in 9-cis betaC with all-trans betaC/9-cis betaC ratios of 2.2, 1.5, 0.6 and 0.4, respectively. Two control supplements, high and low betaC, were prepared from commercial betaC beadlets. The high control supplement had an all-trans/9-cis ratio of 19.0, whereas 9-cis betaC was not detected in the low supplement. On d 27, serum and tissues were obtained for HPLC analysis of betaC and its isomers. Analysis of livers showed that all-trans betaC was the primary isomer present, but 9-cis and other isomers were also detected in all groups. The hepatic all-trans/9-cis ratios were 5.9, 4.9, 2.5, 1.4, 52.2 and47.5, respectively, for the groups listed above. Lower amounts of all-trans and 9-cis betaC were found in kidneys compared with the liver, but ratios of all-trans/9-cis were not different among groups. Only trace amounts of 9-cis betaC were found in serum. These results demonstrate that the algae D. bardawil and D. salina provide a bioavailable source of betaC isomers, but, as in humans, absorption of 9-cis betaC is poor and any 9-cis betaC absorbed is apparently cleared by the liver.     

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.     

Resolution proof transformation for compression and interpolation

Verification methods based on SAT, SMT, and theorem proving often rely on proofs of unsatisfiability as a powerful tool to extract information in order to reduce the overall effort. For example a proof may be traversed to identify a minimal reason that led to unsatisfiability, for computing abstractions, or for deriving Craig interpolants. In this paper we focus on two important aspects that concern efficient handling of proofs of unsatisfiability: compression and manipulation. First of all, since the proof size can be very large in general (exponential in the size of the input problem), it is indeed beneficial to adopt techniques to compress it for further processing. Secondly, proofs can be manipulated as a flexible preprocessing step in preparation for interpolant computation. Both these techniques are implemented in a framework that makes use of local rewriting rules to transform the proofs. We show that a careful use of the rules, combined with existing algorithms, can result in an effective simplification of the original proofs. We have evaluated several heuristics on a wide range of unsatisfiable problems deriving from SAT and SMT test cases.     

Viewfinder Alignment

The viewfinder of a digital camera has traditionally been used for one purpose: to display to the user a preview of what is seen through the camera's lens. High quality cameras are now available on devices such as mobile phones and PDAs, which provide a platform where the camera is a programmable device, enabling applications such as online computational photography, computer vision‐based interactive gaming, and augmented reality. For such online applications, the camera viewfinder provides the user's main interaction with the environment. In this paper, we describe an algorithm for aligning successive viewfinder frames. First, an estimate of inter‐frame translation is computed by aligning integral projections of edges in two images. The estimate is then refined to compute a full 2D similarity transformation by aligning point features. Our algorithm is robust to noise, never requires storing more than one viewfinder frame in memory, and runs at 30 frames per second on standard smartphone hardware. We use viewfinder alignment for panorama capture, low‐light photography, and a camera‐based game controller.