Optimal shapes of compact strings

Optimal geometrical arrangements, such as the stacking of atoms, are of relevance in diverse disciplines. A classic problem is the determination of the optimal arrangement of spheres in three dimensions in order to achieve the highest packing fraction; only recently has it been proved that the answer for infinite systems is a face-centred-cubic lattice. This simply stated problem has had a profound impact in many areas, ranging from the crystallization and melting of atomic systems, to optimal packing of objects and subdivision of space. Here we study an analogous problem--that of determining the optimal shapes of closely packed compact strings. This problem is a mathematical idealization of situations commonly encountered in biology, chemistry and physics, involving the optimal structure of folded polymeric chains. We find that, in cases where boundary effects are not dominant, helices with a particular pitch-radius ratio are selected. Interestingly, the same geometry is observed in helices in naturally-occurring proteins.Comment: 8 pages, 3 composite ps figure

Joint PDF modelling of turbulent flow and dispersion in an urban street canyon

The joint probability density function (PDF) of turbulent velocity and concentration of a passive scalar in an urban street canyon is computed using a newly developed particle-in-cell Monte Carlo method. Compared to moment closures, the PDF methodology provides the full one-point one-time PDF of the underlying fields containing all higher moments and correlations. The small-scale mixing of the scalar released from a concentrated source at the street level is modelled by the interaction by exchange with the conditional mean (IECM) model, with a micro-mixing time scale designed for geometrically complex settings. The boundary layer along no-slip walls (building sides and tops) is fully resolved using an elliptic relaxation technique, which captures the high anisotropy and inhomogeneity of the Reynolds stress tensor in these regions. A less computationally intensive technique based on wall functions to represent boundary layers and its effect on the solution are also explored. The calculated statistics are compared to experimental data and large-eddy simulation. The present work can be considered as the first example of computation of the full joint PDF of velocity and a transported passive scalar in an urban setting. The methodology proves successful in providing high level statistical information on the turbulence and pollutant concentration fields in complex urban scenarios.Comment: Accepted in Boundary-Layer Meteorology, Feb. 19, 200

Increased entropy of signal transduction in the cancer metastasis phenotype

Studies into the statistical properties of biological networks have led to important biological insights, such as the presence of hubs and hierarchical modularity. There is also a growing interest in studying the statistical properties of networks in the context of cancer genomics. However, relatively little is known as to what network features differ between the cancer and normal cell physiologies, or between different cancer cell phenotypes. Based on the observation that frequent genomic alterations underlie a more aggressive cancer phenotype, we asked if such an effect could be detectable as an increase in the randomness of local gene expression patterns. Using a breast cancer gene expression data set and a model network of protein interactions we derive constrained weighted networks defined by a stochastic information flux matrix reflecting expression correlations between interacting proteins. Based on this stochastic matrix we propose and compute an entropy measure that quantifies the degree of randomness in the local pattern of information flux around single genes. By comparing the local entropies in the non-metastatic versus metastatic breast cancer networks, we here show that breast cancers that metastasize are characterised by a small yet significant increase in the degree of randomness of local expression patterns. We validate this result in three additional breast cancer expression data sets and demonstrate that local entropy better characterises the metastatic phenotype than other non-entropy based measures. We show that increases in entropy can be used to identify genes and signalling pathways implicated in breast cancer metastasis. Further exploration of such integrated cancer expression and protein interaction networks will therefore be a fruitful endeavour.Comment: 5 figures, 2 Supplementary Figures and Table

Talk to the Virtual Hands: Self-Animated Avatars Improve Communication in Head-Mounted Display Virtual Environments

Background When we talk to one another face-to-face, body gestures accompany our speech. Motion tracking technology enables us to include body gestures in avatar-mediated communication, by mapping one's movements onto one's own 3D avatar in real time, so the avatar is self-animated. We conducted two experiments to investigate (a) whether head-mounted display virtual reality is useful for researching the influence of body gestures in communication; and (b) whether body gestures are used to help in communicating the meaning of a word. Participants worked in pairs and played a communication game, where one person had to describe the meanings of words to the other. Principal Findings In experiment 1, participants used significantly more hand gestures and successfully described significantly more words when nonverbal communication was available to both participants (i.e. both describing and guessing avatars were self-animated, compared with both avatars in a static neutral pose). Participants ‘passed’ (gave up describing) significantly more words when they were talking to a static avatar (no nonverbal feedback available). In experiment 2, participants' performance was significantly worse when they were talking to an avatar with a prerecorded listening animation, compared with an avatar animated by their partners' real movements. In both experiments participants used significantly more hand gestures when they played the game in the real world. Conclusions Taken together, the studies show how (a) virtual reality can be used to systematically study the influence of body gestures; (b) it is important that nonverbal communication is bidirectional (real nonverbal feedback in addition to nonverbal communication from the describing participant); and (c) there are differences in the amount of body gestures that participants use with and without the head-mounted display, and we discuss possible explanations for this and ideas for future investigation

Compactness Determines the Success of Cube and Octahedron Self-Assembly

Nature utilizes self-assembly to fabricate structures on length scales ranging from the atomic to the macro scale. Self-assembly has emerged as a paradigm in engineering that enables the highly parallel fabrication of complex, and often three-dimensional, structures from basic building blocks. Although there have been several demonstrations of this self-assembly fabrication process, rules that govern a priori design, yield and defect tolerance remain unknown. In this paper, we have designed the first model experimental system for systematically analyzing the influence of geometry on the self-assembly of 200 and 500 µm cubes and octahedra from tethered, multi-component, two-dimensional (2D) nets. We examined the self-assembly of all eleven 2D nets that can fold into cubes and octahedra, and we observed striking correlations between the compactness of the nets and the success of the assembly. Two measures of compactness were used for the nets: the number of vertex or topological connections and the radius of gyration. The success of the self-assembly process was determined by measuring the yield and classifying the defects. Our observation of increased self-assembly success with decreased radius of gyration and increased topological connectivity resembles theoretical models that describe the role of compactness in protein folding. Because of the differences in size and scale between our system and the protein folding system, we postulate that this hypothesis may be more universal to self-assembling systems in general. Apart from being intellectually intriguing, the findings could enable the assembly of more complicated polyhedral structures (e.g. dodecahedra) by allowing a priori selection of a net that might self-assemble with high yields

Triple-negative breast cancer and PTEN (phosphatase and tensin homologue)loss are predictors of BRCA1 germline mutations in women with early-onset and familial breast cancer, but not in women with isolated late-onset breast cancer

Introduction: Given that breast cancers in germline BRCA1 carriers are predominantly estrogen-negative and triple-negative, it has been suggested that women diagnosed with triple-negative breast cancer (TNBC) younger than 50 years should be offered BRCA1 testing, regardless of family cancer characteristics. However, the predictive value of triple-negative breast cancer, when taken in the context of personal and family cancer characteristics, is unknown. The aim of this study was to determine whether TNBC is a predictor of germline BRCA1 mutations, in the context of multiple predictive factors.Methods: Germline mutations in BRCA1 and BRCA2 were analyzed by Sanger sequencing and multiple ligation-dependent probe amplification (MLPA) analysis in 431 women from the Malaysian Breast Cancer Genetic Study, including 110 women with TNBC. Logistic regression was used to identify and to estimate the predictive strength of major determinants. Estrogen receptor (ER) and phosphatase and tensin homologue (PTEN) status were assessed and included in a modified Manchester scoring method.Results: Our study in an Asian series of TNBC patients demonstrated that 27 (24.5%) of 110 patients have germline mutations in BRCA1 (23 of 110) and BRCA2 (four of 110). We found that among women diagnosed with breast cancer aged 36 to 50 years but with no family history of breast or ovarian cancer, the prevalence of BRCA1 and BRCA2 mutations was similar in TNBC (8.5%) and non-TNBC patients (6.7%). By contrast, in women diagnosed with breast cancer, younger than 35 years, with no family history of these cancers, and in women with a family history of breast cancer, the prevalence of mutations was higher in TNBC compared with non-TNBC (28.0% and 9.9%; P = 0.045; and 42.1% and 14.2%; P < 0.0001, respectively]. Finally, we found that incorporation of estrogen-receptor and TNBC status improves the sensitivity of the Manchester Scoring method (42.9% to 64.3%), and furthermore, incorporation of PTEN status further improves sensitivity (42.9% to 85.7%).Conclusions: We found that TNBC is an important criterion for highlighting women who may benefit from genetic testing, but that this may be most useful for women with early-onset breast cancer (35 years or younger) or with a family history of cancers. Furthermore, addition of TNBC and PTEN status improves the sensitivity of the Manchester scoring method and may be particularly important in the Asian context, where risk-assessment models underestimate the number of mutation carriers. © 2012 Phuah et al.; licensee BioMed Central Ltd

Retroperitoneal liposarcomas: The experience of a tertiary Asian center

10.1186/1477-7819-9-12World Journal of Surgical Oncology9

Taking the strain? Impact of glaucoma on patients' informal caregivers

Purpose: To estimate informal caregiver (ICG) strain in people from a glaucoma clinic. Methods: Patients with glaucoma were consecutively identified from a single clinic in England for a cross-sectional postal survey. The sample was deliberately enriched with a number of patients designated as having advanced glaucoma (visual field [VF] mean deviation worse than -12 dB in both eyes). Patients were asked to identify an ICG who recorded a Modified Caregiver Strain Index (MCSI), a validated 13 item instrument scored on a scale of 0-26. Previous research has indicated mean MCSI to be >10 in Multiple Sclerosis and Parkinson’s disease. All participants gave a self-reported measure of general health (EQ5D). Results: Responses from 105 patients (43% of those invited) were analysed; only 38 of the 105 named an ICG. Mean (95% confidence interval [CI]) MCSI was 2.4 (1.3, 3.6) and only three ICGs recorded a MCSI > 7. The percentage of patients with an ICG was much higher in patients with advanced VF loss (82%; 9/11) when compared to those with non-advanced VF loss (31%; 29/94; p=0.001). Mean (standard deviation) MCSI was considerably inflated in the advanced patients (5.6 [4.9] vs 1.5 [2.2] for non-advanced; p=0.040). Worsening VF and poorer self-reported general health (EQ5D) of the patient were associated with worsening MCSI. Conclusion: ICG strain, as measured by MCSI, for patients with non-advanced glaucoma is negligible, compared to other chronic disease. ICG strain increases moderately with worsening VFs but this could be partly explained by worse general health in our sample of patients

Two different point mutations in ABL gene ATP-binding domain conferring Primary Imatinib resistance in a Chronic Myeloid Leukemia (CML) patient: A case report

Imatinib (Gleevec) is the effective therapy for BCR-ABL positive CML patients. Point mutations have been detected in ATP-binding domain of ABL gene which disturbs the binding of Gleevec to this target leading to resistance. Detection of mutations is helpful in clinical management of imatinib resistance. We established a very sensitive (ASO) PCR to detect mutations in an imatinib-resistant CML patient. Mutations C944T and T1052C were detected which cause complete partial imatinib resistance, respectively. This is the first report of multiple point mutations conferring primary imatinib resistance in same patient at the same time. Understanding the biological reasons of primary imatinib resistance is one of the emerging issues of pharmacogenomics and will be helpful in understanding primary resistance of molecularly-targeted cancer therapies. It will also be of great utilization in clinical management of imatinib resistance. Moreover, this ASO-PCR assay is very effective in detecting mutations related to imatinib resistance

Versican G3 Promotes Mouse Mammary Tumor Cell Growth, Migration, and Metastasis by Influencing EGF Receptor Signaling

Increased versican expression in breast tumors is predictive of relapse and has negative impact on survival rates. The C-terminal G3 domain of versican influences local and systemic tumor invasiveness in pre-clinical murine models. However, the mechanism(s) by which G3 influences breast tumor growth and metastasis is not well characterized. Here we evaluated the expression of versican in mouse mammary tumor cell lines observing that 4T1 cells expressed highest levels while 66c14 cells expressed low levels. We exogenously expressed a G3 construct in 66c14 cells and analyzed its effects on cell proliferation, migration, cell cycle progression, and EGFR signaling. Experiments in a syngeneic orthotopic animal model demonstrated that G3 promoted tumor growth and systemic metastasis in vivo. Activation of pERK correlated with high levels of G3 expression. In vitro, G3 enhanced breast cancer cell proliferation and migration by up-regulating EGFR signaling, and enhanced cell motility through chemotactic mechanisms to bone stromal cells, which was prevented by inhibitor AG 1478. G3 expressing cells demonstrated increased CDK2 and GSK-3β (S9P) expression, which were related to cell growth. The activity of G3 on mouse mammary tumor cell growth, migration and its effect on spontaneous metastasis to bone in an orthotopic model was modulated by up-regulating the EGFR-mediated signaling pathway. Taken together, EGFR-signaling appears to be an important pathway in versican G3-mediated breast cancer tumor invasiveness and metastasis