“Dicing and splicing” sphingosine kinase and relevance to cancer

© 2017 by the authors. Licensee MDPI, Basel, Switzerland. Sphingosine kinase (SphK) is a lipid enzyme that maintains cellular lipid homeostasis. Two SphK isozymes, SphK1 and SphK2, are expressed from different chromosomes and several variant isoforms are expressed from each of the isozymes, allowing for the multi-faceted biological diversity of SphK activity. Historically, SphK1 is mainly associated with oncogenicity, however in reality, both SphK1 and SphK2 isozymes possess oncogenic properties and are recognized therapeutic targets. The absence of mutations of SphK in various cancer types has led to the theory that cancer cells develop a dependency on SphK signaling (hyper-SphK signaling) or “non-oncogenic addiction”. Here we discuss additional theories of SphK cellular mislocation and aberrant “dicing and splicing” as contributors to cancer cell biology and as key determinants of the success or failure of SphK/S1P (sphingosine 1 phosphate) based therapeutics

Heart Rate Variability as a Biomarker for Predicting Stroke, Post-stroke Complications and Functionality

© The Author(s) 2018. Background: Heart rate variability (HRV) is a non-invasive measure of the function of the autonomic nervous system, and its dynamic nature may provide a means through which stroke and its associated complications may be predicted, monitored, and managed. Objective: The objective of this review is to identify and provide a critique on the most recent uses of HRV in stroke diagnosis/management and highlight areas that warrant further research. Methods: The MEDLINE, CINAHL, and OVID MEDLINE databases were canvassed using a systematic search strategy, for articles investigating the use of HRV in stroke diagnosis and management. Initial paper selections were based on title alone, and final paper inclusion was informed by a full-text critical appraisal. Results: The systematic search returned 98 records, of which 51 were unique. Following screening, 22 records were included in the final systematic review. The included papers provided some information regarding predicting incident stroke, which largely seems to be best predicted by time- and frequency-domain HRV parameters. Furthermore, post-stroke complications and functionality are similarly predicted by time- and frequency-domain parameters, as well as non-linear parameters in some instances. Conclusions: Current research provides good evidence that HRV parameters may have utility as a biomarker for stroke and for post-stroke complications and/or functionality. Future research would benefit from the integration of non-linear, and novel parameters, the hybridisation of HRV parameters, and the expansion of the utilisation of predictive regression and hazard modelling

On the selection and design of proteins and peptide derivatives for the production of photoluminescent, red-emitting gold quantum clusters

Novel pathways of the synthesis of photoluminescent gold quantum clusters (AuQCs) using biomolecules as reactants provide biocompatible products for biological imaging techniques. In order to rationalize the rules for the preparation of red-emitting AuQCs in aqueous phase using proteins or peptides, the role of different organic structural units was investigated. Three systems were studied: proteins, peptides, and amino acid mixtures, respectively. We have found that cysteine and tyrosine are indispensable residues. The SH/S-S ratio in a single molecule is not a critical factor in the synthesis, but on the other hand, the stoichiometry of cysteine residues and the gold precursor is crucial. These observations indicate the importance of proper chemical behavior of all species in a wide size range extending from the atomic distances (in the AuI-S semi ring) to nanometer distances covering the larger sizes of proteins assuring the hierarchical structure of the whole self-assembled system

Modelling Pricing Policy Based on Shelf-Life of Non Homogeneous Available-To-Promise in Fruit Supply Chains

[EN] Fruit Supply Chains (SCs) are influenced by uncontrollable natural factors causing heterogeneity in their products, as regards certain attributes that are relevant to customers and vary over time because of the shelf-life. As a consequence customers should be served not only with the required quantity and due date as usual, but also with the quality, freshness and homogeneity specified in their orders. The order promising process (OPP) is based on the uncommitted availability of homogeneous product quantities in planned lots (ATP) that are uncertain. Therefore, there is a risk of not being reliable in the commitments because of discrepancies between the real and planned homogeneous quantities. Furthermore, due to the shelf-life (SL), serving customers with the freshest product introduce the risk of increasing waste because of the aging process. To efficiently manage these risks, this work proposes a mathematical model for handling the heterogeneous ATP in fruit SCs and a pricing policy based on the product SL in the moment of delivery. In order to illustrate the application of the modelling approach, a short numerical example is introduced. The example evidences a conflictive situation when optimizing the assignation of homogeneous ATP between serving orders with fresh and more valuable product, what could lead to increase the risk of having waste because of expiration, and consequently, more costs and less profit.This research has been supported by the Ministry of Science, Technology and Telecommunications, government of Costa Rica (MICITT), through the program of innovation and human capital for competitiveness (PINN) (PED-019-2015-1).Grillo-Espinoza, H.; Alemany Díaz, MDM.; Ortiz Bas, Á. (2016). Modelling Pricing Policy Based on Shelf-Life of Non Homogeneous Available-To-Promise in Fruit Supply Chains. IFIP Advances in Information and Communication Technology. 480:608-617. https://doi.org/10.1007/978-3-319-45390-3_52S608617480Alarcon, F., Alemany, M.M.E., Lario, F.C., Oltra, R.F.: The lack of homogeneity in the product (LHP) in the ceramic tile industry and its impact on the reallocation of inventories. Boletin Soc. Espanola Ceram. Vidr. 50, 49–57 (2011). doi: 10.3989/cyv.072011Alemany, M.M.E., Grillo, H., Ortiz, A., Fuertes-Miquel, V.S.: A fuzzy model for shortage planning under uncertainty due to lack of homogeneity in planned production lots. Appl. Math. Model. (2015). doi: 10.1016/j.apm.2014.12.057Alemany, M.M.E., Lario, F.-C., Ortiz, A., Gomez, F.: Available-To-Promise modeling for multi-plant manufacturing characterized by lack of homogeneity in the product: an illustration of a ceramic case. Appl. Math. Model. 37, 3380–3398 (2013). doi: 10.1016/j.apm.2012.07.022Blanco, A.M., Masini, G., Petracci, N., Bandoni, J.A.: Operations management of a packaging plant in the fruit industry. J. Food Eng. 70, 299–307 (2005). doi: 10.1016/j.jfoodeng.2004.05.075Grillo, H., Alemany, M.M.E., Ortiz, A.: A review of mathematical models for supporting the order promising process under Lack of Homogeneity in Product and other sources of uncertainty. Comput. Ind. Eng. 91, 239–261 (2016)Kilic, O.A., van Donk, D.P., Wijngaard, J., Tarim, S.A.: Order acceptance in food processing systems with random raw material requirements. Spectrum 32, 905–925 (2010). doi: 10.1007/s00291-010-0213-4Lin, J.T., Hong, I.H., Wu, C.H., Wang, K.S.: A model for batch available-to-promise in order fulfillment processes for TFT-LCD production chains. Comput. Ind. Eng. 59, 720–729 (2010). doi: 10.1016/j.cie.2010.07.026Maihami, R., Karimi, B.: Optimizing the pricing and replenishment policy for non-instantaneous deteriorating items with stochastic demand and promotional efforts. Comput. Oper. Res. 51, 302–312 (2014). doi: 10.1016/j.cor.2014.05.022Mundi, M.I., Alemany, M.M.E., Poler, R., Fuertes-Miquel, V.S.: Fuzzy sets to model master production effectively in Make to Stock companies with Lack of Homogeneity in the Product. Fuzzy Sets Syst. 293, 95–112 (2016). http://dx.doi.org/10.1016/j.fss.2015.06.009Tsao, Y.-C., Sheen, G.-J.: Dynamic pricing, promotion and replenishment policies for a deteriorating item under permissible delay in payments. Part Spec. Issue Top. Real-Time Supply Chain Manag. 35, 3562–3580 (2008). doi: 10.1016/j.cor.2007.01.02

Prognostic relevance of a T-type calcium channels gene signature in solid tumours: A correlation ready for clinical validation

BackgroundT-type calcium channels (TTCCs) mediate calcium influx across the cell membrane. TTCCs regulate numerous physiological processes including cardiac pacemaking and neuronal activity. In addition, they have been implicated in the proliferation, migration and differentiation of tumour tissues. Although the signalling events downstream of TTCC-mediated calcium influx are not fully elucidated, it is clear that variations in the expression of TTCCs promote tumour formation and hinder response to treatment.MethodsWe examined the expression of TTCC genes (all three subtypes; CACNA-1G, CACNA-1H and CACNA-1I) and their prognostic value in three major solid tumours (i.e. gastric, lung and ovarian cancers) via a publicly accessible database.ResultsIn gastric cancer, expression of all the CACNA genes was associated with overall survival (OS) among stage I-IV patients (all pConclusionsAlterations in CACNA gene expression are linked to tumour prognosis. Gastric cancer represents the most promising setting for further evaluation

Input-to-state stability of infinite-dimensional control systems

We develop tools for investigation of input-to-state stability (ISS) of infinite-dimensional control systems. We show that for certain classes of admissible inputs the existence of an ISS-Lyapunov function implies the input-to-state stability of a system. Then for the case of systems described by abstract equations in Banach spaces we develop two methods of construction of local and global ISS-Lyapunov functions. We prove a linearization principle that allows a construction of a local ISS-Lyapunov function for a system which linear approximation is ISS. In order to study interconnections of nonlinear infinite-dimensional systems, we generalize the small-gain theorem to the case of infinite-dimensional systems and provide a way to construct an ISS-Lyapunov function for an entire interconnection, if ISS-Lyapunov functions for subsystems are known and the small-gain condition is satisfied. We illustrate the theory on examples of linear and semilinear reaction-diffusion equations.Comment: 33 page

Flat bands as a route to high-temperature superconductivity in graphite

Superconductivity is traditionally viewed as a low-temperature phenomenon. Within the BCS theory this is understood to result from the fact that the pairing of electrons takes place only close to the usually two-dimensional Fermi surface residing at a finite chemical potential. Because of this, the critical temperature is exponentially suppressed compared to the microscopic energy scales. On the other hand, pairing electrons around a dispersionless (flat) energy band leads to very strong superconductivity, with a mean-field critical temperature linearly proportional to the microscopic coupling constant. The prize to be paid is that flat bands can generally be generated only on surfaces and interfaces, where high-temperature superconductivity would show up. The flat-band character and the low dimensionality also mean that despite the high critical temperature such a superconducting state would be subject to strong fluctuations. Here we discuss the topological and non-topological flat bands discussed in different systems, and show that graphite is a good candidate for showing high-temperature flat-band interface superconductivity.Comment: Submitted as a chapter to the book on "Basic Physics of functionalized Graphite", 21 pages, 12 figure

Pleiotropic functions of the tumor- and metastasis-suppressing Matrix Metalloproteinase-8 in mammary cancer in MMTV-PyMT transgenic mice

Matrix metalloproteinase-8 (MMP-8; neutrophil collagenase) is an important regulator of innate immunity which has onco-suppressive actions in numerous tumor types

The relationship between the systemic inflammatory response, tumour proliferative activity, T-lymphocytic and macrophage infiltration, microvessel density and survival in patients with primary operable breast cancer

The significance of the inter-relationship between tumour and host local/systemic inflammatory responses in primary operable invasive breast cancer is limited. The inter-relationship between the systemic inflammatory response (pre-operative white cell count, C-reactive protein and albumin concentrations), standard clinicopathological factors, tumour T-lymphocytic (CD4+ and CD8+) and macrophage (CD68+) infiltration, proliferative (Ki-67) index and microvessel density (CD34+) was examined using immunohistochemistry and slide-counting techniques, and their prognostic values were examined in 168 patients with potentially curative resection of early-stage invasive breast cancer. Increased tumour grade and proliferative activity were associated with greater tumour T-lymphocyte (P<0.05) and macrophage (P<0.05) infiltration and microvessel density (P<0.01). The median follow-up of survivors was 72 months. During this period, 31 patients died; 18 died of their cancer. On univariate analysis, increased lymph-node involvement (P<0.01), negative hormonal receptor (P<0.10), lower albumin concentrations (P<0.01), increased tumour proliferation (P<0.05), increased tumour microvessel density (P<0.05), the extent of locoregional control (P<0.0001) and limited systemic treatment (Pless than or equal to0.01) were associated with cancer-specific survival. On multivariate analysis of these significant covariates, albumin (HR 4.77, 95% CI 1.35–16.85, P=0.015), locoregional treatment (HR 3.64, 95% CI 1.04–12.72, P=0.043) and systemic treatment (HR 2.29, 95% CI 1.23–4.27, P=0.009) were significant independent predictors of cancer-specific survival. Among tumour-based inflammatory factors, only tumour microvessel density (P<0.05) was independently associated with poorer cancer-specific survival. The host inflammatory responses are closely associated with poor tumour differentiation, proliferation and malignant disease progression in breast cancer

Observation of inhibited electron-ion coupling in strongly heated graphite

Creating non-equilibrium states of matter with highly unequal electron and lattice temperatures (Tele≠Tion) allows unsurpassed insight into the dynamic coupling between electrons and ions through time-resolved energy relaxation measurements. Recent studies on low-temperature laser-heated graphite suggest a complex energy exchange when compared to other materials. To avoid problems related to surface preparation, crystal quality and poor understanding of the energy deposition and transport mechanisms, we apply a different energy deposition mechanism, via laser-accelerated protons, to isochorically and non-radiatively heat macroscopic graphite samples up to temperatures close to the melting threshold. Using time-resolved x ray diffraction, we show clear evidence of a very small electron-ion energy transfer, yielding approximately three times longer relaxation times than previously reported. This is indicative of the existence of an energy transfer bottleneck in non-equilibrium warm dense matter