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.     

Tree-structured piecewise linear adaptive equalization

The use of a tree-structured piecewise linear filter as an adaptive equalizer is proposed. In the tree equalizer, each node in a tree is associated with a linear filter restricted to a polygonal domain, and each subtree is associated with a piecewise linear filter. A training sequence is used to adaptively update the filter coefficients and domains at each node, and to select the best subtree and corresponding piecewise linear filter. The tree-structured approach offers several advantages. First, it makes use of standard linear adaptive filtering techniques at each node to find the corresponding conditional linear filter. Second, it allows for efficient selection of the subtree and corresponding piecewise linear filter of appropriate complexity. Overall, the approach is computationally efficient and conceptually simple. Numerical experiments are performed to show the advantages of tree-structured piecewise linear and piecewise decision feedback equalizers over linear, polynomial, and decision feedback equalizers for the equalization of channels with severe intersymbol interference     

Comparison between morphologic changes seen on high-resolution CT and regional pulmonary perfusion seen on SPECT in patients with cystic fibrosis

OBJECTIVE: To evaluate the relationship between morphologic findings seen on high-resolution computed tomography (HRCT) of the lung and regional lung perfusion depicted on single photon-emission computed tomography (SPECT) pulmonary perfusion imaging in patients with cystic fibrosis. MATERIALS AND METHODS: Ten HRCT and 10 technetium-99 m macroaggregated albumin SPECT pulmonary perfusion imaging studies were performed on eight young adult patients who were considered to be clinically well and have mild to moderate cystic fibrosis. HRCT scans of the chest were evaluated using a CT scoring system which included grading of bronchiectasis, peribronchial thickening, hyperlucency, bullae, collapse/consolidation, and mucus plugging. Each lung was divided into six anatomic zones which were independently scored. A lung perfusion score (between 0 and 100), reflecting the percentage of compromised lung, was estimated for each zone. Axial lung perfusion SPECT images were matched anatomically to HRCT images. Lung function was considered compromised when the counts per pixel were less than 25 % of the count level seen in an area of the same patient's lung which was judged to be normal. RESULTS: There was a statistically significant relationship (P = 0.0001) between HRCT total scores and SPECT lung perfusion scores as well as between hyperlucency scores by HRCT and the SPECT lung perfusion scores. However, the HRCT score was a poor predictor of the lung perfusion score in zones with intermediate HRCT scores, which constituted 106 of 120 zones. CONCLUSION: Morphologic changes depicted by HRCT correlate with decreased lung pefusion on SPECT. However, HRCT changes accurately predict regional lung function only in the most normal and severely diseased lung zones.     

Methotrexate treatment of idiopathic granulomatous hepatitis

OBJECTIVE: To test the efficacy and safety of low-dose oral pulse methotrexate therapy in patients with idiopathic granulomatous hepatitis who had complications of, did not respond to, or refused glucocorticoid therapy. DESIGN: Prospective case study. SETTING: Academic medical center hospital. PATIENTS: Seven patients with biopsy-proven, idiopathic granulomatous hepatitis who could not tolerate or were unresponsive to glucocorticoid therapy. INTERVENTION: Low-dose oral pulse methotrexate, 15 mg/wk. MEASUREMENTS: Temperature, symptoms, dose of concurrent glucocorticoids, biochemical tests of liver function, side effects of methotrexate, and assessment of liver biopsy specimens. RESULTS: All six febrile patients became afebrile within 3 months of starting methotrexate. Fatigue and anorexia improved in all patients. Glucocorticoid therapy was successfully discontinued within 6 months of starting methotrexate in four patients receiving prednisone at entry. Liver biopsy specimens were obtained again after methotrexate therapy and showed absence of granulomas in four of four patients. The minimum effective dose of methotrexate was 0.20 mg/kg body weight per week. No serious adverse effects and no failures to respond to methotrexate therapy were noted in this group of patients. In three patients, methotrexate therapy has been successfully tapered without signs or symptoms of recurrent disease. CONCLUSIONS: Low-dose oral pulse methotrexate was effective in treating patients with granulomatous hepatitis.     

Regulation of organelle movement in melanophores by protein kinase A (PKA), protein kinase C (PKC), and protein phosphatase 2A (PP2A)

We used melanophores, cells specialized for regulated organelle transport, to study signaling pathways involved in the regulation of transport. We transfected immortalized Xenopus melanophores with plasmids encoding epitope-tagged inhibitors of protein phosphatases and protein kinases or control plasmids encoding inactive analogues of these inhibitors. Expression of a recombinant inhibitor of protein kinase A (PKA) results in spontaneous pigment aggregation. alpha-Melanocyte-stimulating hormone (MSH), a stimulus which increases intracellular cAMP, cannot disperse pigment in these cells. However, melanosomes in these cells can be partially dispersed by PMA, an activator of protein kinase C (PKC). When a recombinant inhibitor of PKC is expressed in melanophores, PMA-induced pigment dispersion is inhibited, but not dispersion induced by MSH. We conclude that PKA and PKC activate two different pathways for melanosome dispersion. When melanophores express the small t antigen of SV-40 virus, a specific inhibitor of protein phosphatase 2A (PP2A), aggregation is completely prevented. Conversely, overexpression of PP2A inhibits pigment dispersion by MSH. Inhibitors of protein phosphatase 1 and protein phosphatase 2B (PP2B) do not affect pigment movement. Therefore, melanosome aggregation is mediated by PP2A.     

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.     

Finite-size effects in surface tension: Thermodynamics and the Gaussian interface model

It has been suggested by Kayser that finite-size effects associated with capillary waves might play a significant role in some surface tension measurements; for capillary rise between plates a distance D apart, an effect varying as 1/D and apparently observable in measurements, was proposed. In reconsidering this problem, one must analyze the thermodynamics of finite-size corrections to surface tension. In particular, one sees that capillary rise between plates does not measure the interfacial free energy density but, rather, a derivative of the interfacial free energy with respect to a system dimension. The quantity needed to draw definite conclusions, the finite-size residual free energy, can be calculated within the harmonic or Gaussian capillary wave model in d spatial dimensions with the aid of Poisson summation techniques and should yield the correct leading asymptotic behavior. For d=3 and experimentally relevant parameter values, the results are independent of the short-wavelength cutoff needed in the model and can be checked against the theory of conformai covariance at two-dimensional critical points. It is found that the finite-size effects in capillary-rise measurements of surface tension vary as 1/D ² (with a universal coefficient) but are too small to be seen in current experiments.Invited paper presented at the Tenth Symposium on Thermophysical Properties, June 20–23, 1988, Gaithersburg, Maryland, U.S.A.     

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.