BIT-LEVEL SYSTOLIC ARRAY CIRCUIT FOR MATRIX VECTOR MULTIPLICATION.

A bit-level systolic array for computing matrix x vector products is described. The operation is carried out on bit parallel input data words and the basic circuit takes the form of a 1-bit slice. Several bit-slice components must be connected together to form the final result, and authors outline two different ways in which this can be done. The basic array also has considerable potential as a stand-alone device, and its use in computing the Walsh-Hadamard transform and discrete Fourier transform operations is briefly discussed.

Multiple Biomarkers for the prediction of ischemic stroke: the PRIME study

Objective: To simultaneously evaluate 14 biomarkers from distinct biological pathways for risk prediction of ischemic stroke, including biomarkers of hemostasis, inflammation, and endothelial activation as well as chemokines and adipocytokines.
Methods and Results: The Prospective Epidemiological Study on Myocardial Infarction (PRIME) is a cohort of 9771 healthy men 50 to 59 years of age who were followed up over 10 years. In a nested case–control study, 95 ischemic stroke cases were matched with 190 controls. After multivariable adjustment for traditional risk factors, fibrinogen (odds ratio [OR], 1.53; 95% confidence interval [CI], 1.03–2.28), E-selectin (OR, 1.76; 95% CI, 1.06–2.93), interferon-γ-inducible-protein-10 (OR, 1.72; 95% CI, 1.06–2.78), resistin (OR, 2.86; 95% CI, 1.30–6.27), and total adiponectin (OR, 1.82; 95% CI, 1.04–3.19) were significantly associated with ischemic stroke. Adding E-selectin and resistin to a traditional risk factor model significantly increased the area under the receiver-operating characteristic curve from 0.679 (95% CI, 0.612–0.745) to 0.785 and 0.788, respectively, and yielded a categorical net reclassification improvement of 29.9% (P=0.001) and 28.4% (P=0.002), respectively. Their simultaneous inclusion in the traditional risk factor model increased the area under the receiver-operating characteristic curve to 0.824 (95% CI, 0.770–0.877) and resulted in an net reclassification improvement of 41.4% (P<0.001). Results were confirmed when using continuous net reclassification improvement.
Conclusion: Among multiple biomarkers from distinct biological pathways, E-selectin and resistin provided incremental and additive value to traditional risk factors in predicting ischemic stroke.

Population Mobility Dynamics Estimated from Mobile Telephony Data

In the last decade, mobile phones and mobile devices using mobile cellular telecommunication network connections have become ubiquitous. In several developed countries, the penetration of such devices has surpassed 100 percent. They facilitate communication and access to large quantities of data without the requirement of a fixed location or connection. Assuming mobile phones usually are in close proximity with the user, their cellular activities and locations are indicative of the user's activities and movements. As such, those cellular devices may be considered as a large scale distributed human activity sensing platform. This paper uses mobile operator telephony data to visualize the regional flows of people across the Republic of Ireland. In addition, the use of modified Markov chains for the ranking of significant regions of interest to mobile subscribers is investigated. Methodology is then presented which demonstrates how the ranking of significant regions of interest may be used to estimate national population, results of which are found to have strong correlation with census data.

Three-dimensional modeling of the human fallopian tube fimbriae

OBJECTIVE: Ovarian cancer is the most lethal gynecological malignancy that affects women. Recent data suggests that the disease may originate in the fallopian fimbriae; however, the anatomical origin of ovarian carcinogenesis remains unclear. This is largely driven by our lack of knowledge regarding the structure and function of normal fimbriae and the relative paucity of models that accurately recapitulate the in vivo fallopian tube. Therefore, a human three-dimensional (3D) culture system was developed to examine the role of the fallopian fimbriae in serous tumorigenesis.

METHODS: Alginate matrix was utilized to support human fallopian fimbriae ex vivo. Fimbriae were cultured with factors hypothesized to contribute to carcinogenesis, namely; H2O2 (1mM) a mimetic of oxidative stress, insulin (5μg/ml) to stimulate glycolysis, and estradiol (E2, 10nM) which peaks before ovulation. Cultures were evaluated for changes in proliferation and p53 expression, criteria utilized to identify potential precursor lesions. Further, secretory factors were assessed after treatment with E2 to identify if steroid signaling induces a pro-tumorigenic microenvironment.

RESULTS: 3D fimbriae cultures maintained normal tissue architecture up to 7days, retaining both epithelial subtypes. Treatment of cultures with H2O2 or insulin significantly induced proliferation. However, p53 stabilization was unaffected by any particular treatment, although it was induced by ex vivo culturing. Moreover, E2-alone treatment significantly induced its canonical target PR and expression of IL8, a factor linked to poor outcome.

CONCLUSIONS: 3D alginate cultures of human fallopian fimbriae provide an important microphysiological model, which can be further utilized to investigate serous tumorigenesis originating from the fallopian tube.

B-spline methods in R-matrix theory for scattering in two-electron systems

The use of B-spline basis sets in R-matrix theory for scattering processes has been investigated. In the present approach a B-spline basis is used for the description of the inner region, which is matched to the physical outgoing wavefunctions by the R-matrix. Using B-splines, continuum basis functions can be determined easily, while pseudostates can be included naturally. The accuracy for low-energy scattering processes is demonstrated by calculating inelastic scattering cross sections for e colliding on H. Very good agreement with other calculations has been obtained. Further extensions of the codes to quasi two-electron systems and general atoms are discussed as well as the application to (multi) photoionization.

Children with stable asthma have reduced airway matrix metalloproteinase-9 and matrix metalloproteinase-9/tissue inhibitor of metalloproteinase-1 ratio

Background Childhood asthma is characterized by inflammation of the airways. Structural changes of the airway wall may also be seen in some children early in the course of the disease. Matrix metalloproteinases (MMPs) are key mediators in the metabolism of the extracellular matrix (ECM). Objective To investigate the balance of MMP-8, MMP-9 and tissue inhibitor of metalloproteinases (TIMP)-1 in the airways of children with asthma. Methods One hundred and twenty-four children undergoing elective surgical procedures also underwent non-bronchoscopic bronchoalveolar lavage (BAL). MMP-8, MMP-9 and TIMP-1 were measured by ELISA. Results There was a significant reduction in MMP-9 in atopic asthmatic children (n=31) compared with normal children (n=30) [median difference: 0.57 ng/mL (95% confidence interval: 0.18–1.1 ng/mL)]. The ratio of MMP-9 to TIMP-1 was also reduced in asthmatic children. Levels of all three proteins were significantly correlated to each other and to the relative proportions of particular inflammatory cells in BAL fluid (BALF). Both MMP-8 and MMP-9 were moderately strongly correlated to the percentage neutrophil count (r=0.40 and 0.47, respectively, P

Alterations in vascular matrix metalloproteinase due to ageing and chronic hypertension: effects of endothelin receptor blockade.

OBJECTIVE: To determine the effects of age and dual endothelin (ET)A/ETB receptor antagonism (bosentan) on aortic matrix metalloproteinase (MMP) abundance and tissue inhibitor of metalloproteinase (TIMP) expression in normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR). METHODS: Male SHR and control WKY rats were randomly assigned to receive placebo or bosentan (100 mg/kg per day) for 3 months. Animals were killed under terminal anaesthesia at either 20 weeks (adult) or 17-20 months (senescent). Aortic gelatinase activity was determined by zymography, whereas MT-1 MMP and TIMP-1 expression were assessed by immunoblotting. RESULTS: In WKY rats, aortic MMP-2 but not proMMP-2 activity was 3.6-fold higher (P <0.02) in the senescent compared with the adult group. TIMP-1 (twofold) and MT-1 MMP (3.8-fold) expression increased (P <0.05) with age in the WKY groups. Short-term hypertension (adult SHR versus adult WKY) increased MMP-2 to 74.7 +/- 14.1 from 18.9 +/- 3.5 arbitrary units (AU) (P = 0.0012), but did not alter proMMP-2 activity. This increased further on progression to chronic hypertension (117.4 +/- 12.2 versus 74.7 +/- 14.1 AU; P <0.02). Bosentan decreased MMP-2 (78.9 +/- 3.8 versus 117.4 +/- 12.2 AU; P = 0.014) and proMMP-2 activity (P <0.006) in the senescent SHR group. CONCLUSION: Ageing and the development/progression of hypertension are associated with increased MMP-2 activity in the aorta, which is consistent with ongoing remodelling of the vasculature. However, the underlying mechanisms regulating MMP-2 abundance in ageing and hypertension appear to be divergent, as MT-1 MMP expression is differentially altered. Dual ETA/ETB receptor antagonism did not alter the age-dependent increase in aortic MMP activity in normotensive rats. However, bosentan decreased pro and active MMP-2 activity in senescent SHR rats, indicating that ET modulates late events in vascular remodelling in hypertension.

Entanglement generation in harmonic chains: Tagging by squeezing

We address the problem of springlike coupling between bosons in an open-chain configuration where the counter-rotating terms are explicitly included. We show that fruitful insight can be gained by decomposing the time-evolution operator of this problem into a pattern of linear-optics elements. This allows us to provide a clear picture of the effects of the counter-rotating terms in the important problem of long-haul entanglement distribution. The analytic control over the variance matrix of the state of the bosonic register allows us to track the dynamics of the entanglement. This helps in designing a global addressing scheme, complemented by a proper initialization of the register, which quantitatively improves the entanglement between the extremal oscillators in the chain, thus providing a strategy for feasible long-distance entanglement distribution.

A new Jacobian matrix for optimal learning of single-layer neural networks

This paper investigates the learning of a wide class of single-hidden-layer feedforward neural networks (SLFNs) with two sets of adjustable parameters, i.e., the nonlinear parameters in the hidden nodes and the linear output weights. The main objective is to both speed up the convergence of second-order learning algorithms such as Levenberg-Marquardt (LM), as well as to improve the network performance. This is achieved here by reducing the dimension of the solution space and by introducing a new Jacobian matrix. Unlike conventional supervised learning methods which optimize these two sets of parameters simultaneously, the linear output weights are first converted into dependent parameters, thereby removing the need for their explicit computation. Consequently, the neural network (NN) learning is performed over a solution space of reduced dimension. A new Jacobian matrix is then proposed for use with the popular second-order learning methods in order to achieve a more accurate approximation of the cost function. The efficacy of the proposed method is shown through an analysis of the computational complexity and by presenting simulation results from four different examples.

Breit-Pauli R-matrix calculation of fine-structure effective collision strengths for the electron impact excitation of Mg V

Context. Electron-impact excitation collision strengths are required for the analysis and interpretation of stellar observations.
Aims. This calculation aims to provide effective collision strengths for the Mg V ion for a larger number of transitions and for a greater temperature range than previously available, using collision strength data that include contributions from resonances.
Methods. A 19-state Breit-Pauli R-matrix calculation was performed. The target states are represented by configuration interaction wavefunctions and consist of the 19 lowest LS states, having configurations 2s22p4, 2s2p5, 2p6, 2s22p33s, and 2s22p33p. These target states give rise to 37 fine-structure levels and 666 possible transitions. The effective collision strengths were calculated by averaging the electron collision strengths over a Maxwellian distribution of electron velocities.
Results. The non-zero effective collision strengths for transitions between the fine-structure levels are given for electron temperatures in the range = 3.0 - 7.0. Data for transitions among the 5 fine-structure levels arising from the 2s22p4 ground state configurations, seen in the UV range, are discussed in the paper, along with transitions in the EUV range – transitions from the ground state 3P levels to 2s2p5?3P levels. The 2s22p4?1D–2s2p5?1P transition is also noted. Data for the remaining transitions are available at the CDS.

Alpha-1-antitrypsin aerosolized augmentation abrogates neutrophil elastase-induced expression of cathepsin B and matrix metalloprotease 2 in vivo and in vitro

Background: Neutrophil elastase (NE) activity is increased in lung diseases such as a1-antitrypsin (A1AT) deficiency and pneumonia. It has recently been shown to induce expression of cathepsin B and matrix metalloprotease 2 (MMP-2) in vitro and in a mouse model. It is postulated that increased cathepsin B and MMP-2 in acute and chronic lung diseases result from high levels of extracellular NE and that expression of these proteases could be inhibited by A1AT augmentation therapy.

Methods: Cathepsin and MMP activities were assessed in bronchoalveolar lavage (BAL) fluid from patients with A1AT deficiency, pneumonia and control subjects. Macrophages were exposed to BAL fluid rich in free NE from patients with pneumonia following pretreatment with A1AT. MMP-2, cathepsin B, secretory leucoprotease inhibitor (SLPI) and lactoferrin levels were determined in BAL fluid from A1AT-deficient patients before and after aerosolisation of A1AT.

Results: BAL fluid from both patients with pneumonia and those with A1AT deficiency containing free NE had increased cathepsin B and MMP-2 activities compared with BAL fluid from healthy volunteers. The addition of A1AT to BAL fluid from patients with pneumonia greatly reduced NE-induced cathepsin B and MMP-2 expression in macrophages in vitro. A1AT augmentation therapy to A1AT-deficient individuals also reduced cathepsin B and MMP-2 activity in BAL fluid in vivo. Furthermore, A1AT-deficient patients had higher levels of SLPI and lactoferrin after A1AT augmentation therapy.

Conclusion: These findings suggest a novel role for A1AT inhibition of NE-induced upregulation of MMP and cathepsin expression both in vitro and in vivo.

Advanced glycation end products cause increased CCN family and extracellular matrix gene expression in the diabetic rodent retina

Aims/hypothesis: Referred to as CCN, the family of growth factors consisting of cystein-rich protein 61 (CYR61, also known as CCN1), connective tissue growth factor (CTGF, also known as CCN2), nephroblastoma overexpressed gene (NOV, also known as CCN3) and WNT1-inducible signalling pathway proteins 1, 2 and 3 (WISP1, -2 and -3; also known as CCN4, -5 and -6) affects cellular growth, differentiation, adhesion and locomotion in wound repair, fibrotic disorders, inflammation and angiogenesis. AGEs formed in the diabetic milieu affect the same processes, leading to diabetic complications including diabetic retinopathy. We hypothesised that pathological effects of AGEs in the diabetic retina are a consequence of AGE-induced alterations in CCN family expression.

Materials and methods: CCN gene expression levels were studied at the mRNA and protein level in retinas of control and diabetic rats using real-time quantitative PCR, western blotting and immunohistochemistry at 6 and 12 weeks of streptozotocin-induced diabetes in the presence or absence of aminoguanidine, an AGE inhibitor. In addition, C57BL/6 mice were repeatedly injected with exogenously formed AGE to establish whether AGE modulate retinal CCN growth factors in vivo.

Results: After 6 weeks of diabetes, Cyr61 expression levels were increased more than threefold. At 12 weeks of diabetes, Ctgf expression levels were increased twofold. Treatment with aminoguanidine inhibited Cyr61 and Ctgf expression in diabetic rats, with reductions of 31 and 36%, respectively, compared with untreated animals. Western blotting showed a twofold increase in CTGF production, which was prevented by aminoguanidine treatment. In mice infused with exogenous AGE, Cyr61 expression increased fourfold and Ctgf expression increased twofold in the retina.

Conclusions/interpolation: CTGF and CYR61 are downstream effectors of AGE in the diabetic retina, implicating them as possible targets for future intervention strategies against the development of diabetic retinopathy.