Genetic variation in the LDL receptor-related protein 5 (LRP5) gene : Association with bone health and metabolic parameters

Bone mass accrual and maintenance are regulated by a complex interplay between genetic and environmental factors. Recent studies have revealed an important role for the low-density lipoprotein receptor-related protein 5 (LRP5) in this process. The aim of this thesis study was to identify novel variants in the LRP5 gene and to further elucidate the association of LRP5 and its variants with various bone health related clinical characteristics. The results of our studies show that loss-of-function mutations in LRP5 cause severe osteoporosis not only in homozygous subjects but also in the carriers of these mutations, who have significantly reduced bone mineral density (BMD) and increased susceptibility to fractures. In addition, we demonstrated for the first time that a common polymorphic LRP5 variant (p.A1330V) was associated with reduced peak bone mass, an important determinant of BMD and osteoporosis in later life. The results from these two studies are concordant with results seen in other studies on LRP5 mutations and in association studies linking genetic variation in LRP5 with BMD and osteoporosis. Several rare LRP5 variants were identified in children with recurrent fractures. Sequencing and multiplex ligation-dependent probe amplification (MLPA) analyses revealed no disease-causing mutations or whole-exon deletions. Our findings from clinical assessments and family-based genotype-phenotype studies suggested that the rare LRP5 variants identified are not the definite cause of fractures in these children. Clinical assessments of our study subjects with LPR5 mutations revealed an unexpectedly high prevalence of impaired glucose tolerance and dyslipidaemia. Moreover, in subsequent studies we discovered that common polymorphic LRP5 variants are associated with unfavorable metabolic characteristics. Changes in lipid profile were already apparent in pre-pubertal children. These results, together with the findings from other studies, suggest an important role for LRP5 also in glucose and lipid metabolism. Our results underscore the important role of LRP5 not only in bone mass accrual and maintenance of skeletal health but also in glucose and lipid metabolism. The role of LRP5 in bone metabolism has long been studied, but further studies with larger study cohorts are still needed to evaluate the specific role of LRP5 variants as metabolic risk factors.

An evaluation of rate-controlling obstacles for low-temperature deformation of zirconium

The low-temperature plastic flow of alpha-zirconium was studied by employing constantrate tensile tests and differential-stress creep experiments. The activation parameters, enthalpy and area, have been obtained as a function of stress for pure, as well as commercial zirconium. The activation area is independent of grain size and purity and falls to about 9b2 at high stresses. The deformation mechanism below about 700° K is found to be controlled by a single thermally activated process, and not a two-stage activation mechanism. Several dislocation mechanisms are examined and it is concluded that overcoming the Peierls energy humps by the formation of kink pairs in a length of dislocation is the rate-controlling mechanism. The total energy needed to nucleate a double kink is about 0.8 eV in pure zirconium and 1 eV in commercial zirconium

High Rate Capability of Porous LiNi1/3Co1/3Mn1/3O2 Synthesized by Polymer Template Route

Layered LiNi1/3Co1/3Mn1/3O2, which is isostructural with LiCoO2, is considered as a potential cathode material for Li-ion batteries. Submicrometer sized porous particles are useful for high discharge rates. The present work involves a synthesis of submicrometer sized porous particles of LiNi1/3Co1/3Mn1/3O2 using a triblock copolymer as a soft template. The precursor obtained from the reaction is heated at different temperatures between 600 and 900 degrees C for 6 h to get the final product samples. The compound attains increased crystallinity with an increase in the temperature of preparation. However, there is a decrease in the surface area and also in the porosity of the sample. Nevertheless, the LiNi1/3Co1/3Mn1/3O2 sample prepared at 900 degrees C exhibits a high rate capability and stable capacity retention on cycling. The electrochemical performance of LiNi1/3Co1/3Mn1/3O2 prepared in the absence of the polymer template is inferior to that of the sample prepared in the presence of the polymer template. (C) 2010 The Electrochemical Society. [DOI: 10.1149/1.3364944] All rights reserved.

Solution-Combustion Synthesized Nanocrystalline Li4Ti5O12 As High-Rate Performance Li-Ion Battery Anode

Nanocrystalline Li4Ti5O12 (LTO) crystallizing in cubic spinel-phase has been synthesized by single-step-solution-combustion method in less than one minute. LTO particles thus synthesized are flaky and highly porous in nature with a surface area of 12 m(2)/g. Transmission electron micrographs indicate the primary particles to be agglomerated crystallites of varying size between 20 and 50 nm with a 3-dimensional interconnected porous network. During their galvanostatic charge-discharge at varying rates, LTO electrodes yield a capacity value close to the theoretical value of 175 mA h/g at C/2 rate. The electrodes also exhibit promising capacity retention with little capacity loss over 100 cycles at varying discharge rates together with attractive discharge-rate capabilities yielding capacity values of 140 mA h/g and 70 mA h/g at 10 and 100 C discharge rates, respectively. The ameliorated electrode-performance is ascribed to nano and highly porous morphology of the electrodes that provide short diffusion-paths for Li in conjunction with electrolyte percolation through the electrode pores ensuring a high flux of Li.

On the maximal rate of (n+1) x n and (n+2) x n complex orthogonal designs

For p x n complex orthogonal designs in k variables, where p is the number of channels uses and n is the number of transmit antennas, the maximal rate L of the design is asymptotically half as n increases. But, for such maximal rate codes, the decoding delay p increases exponentially. To control the delay, if we put the restriction that p = n, i.e., consider only the square designs, then, the rate decreases exponentially as n increases. This necessitates the study of the maximal rate of the designs with restrictions of the form p = n+1, p = n+2, p = n+3 etc. In this paper, we study the maximal rate of complex orthogonal designs with the restrictions p = n+1 and p = n+2. We derive upper and lower bounds for the maximal rate for p = n+1 and p = n+2. Also for the case of p = n+1, we show that if the orthogonal design admit only the variables, their negatives and multiples of these by root-1 and zeros as the entries of the matrix (other complex linear combinations are not allowed), then the maximal rate always equals the lower bound.

Minimum-Decoding-Complexity, maximum-rate Space-Time Block Codes from Clifford algebras

It is well known that Alamouti code and, in general, Space-Time Block Codes (STBCs) from complex orthogonal designs (CODs) are single-symbol decodable/symbolby-symbol decodable (SSD) and are obtainable from unitary matrix representations of Clifford algebras. However, SSD codes are obtainable from designs that are not CODs. Recently, two such classes of SSD codes have been studied: (i) Coordinate Interleaved Orthogonal Designs (CIODs) and (ii) Minimum-Decoding-Complexity (MDC) STBCs from Quasi-ODs (QODs). In this paper, we obtain SSD codes with unitary weight matrices (but not CON) from matrix representations of Clifford algebras. Moreover, we derive an upper bound on the rate of SSD codes with unitary weight matrices and show that our codes meet this bound. Also, we present conditions on the signal sets which ensure full-diversity and give expressions for the coding gain.

Design and analysis of rate aware ad hoc 802.11 networks

802.11 WLANs are characterized by high bit error rate and frequent changes in network topology. The key feature that distinguishes WLANs from wired networks is the multi-rate transmission capability, which helps to accommodate a wide range of channel conditions. This has a significant impact on higher layers such as routing and transport levels. While many WLAN products provide rate control at the hardware level to adapt to the channel conditions, some chipsets like Atheros do not have support for automatic rate control. We first present a design and implementation of an FER-based automatic rate control state machine, which utilizes the statistics available at the device driver to find the optimal rate. The results show that the proposed rate switching mechanism adapts quite fast to the channel conditions. The hop count metric used by current routing protocols has proven itself for single rate networks. But it fails to take into account other important factors in a multi-rate network environment. We propose transmission time as a better path quality metric to guide routing decisions. It incorporates the effects of contention for the channel, the air time to send the data and the asymmetry of links. In this paper, we present a new design for a multi-rate mechanism as well as a new routing metric that is responsive to the rate. We address the issues involved in using transmission time as a metric and presents a comparison of the performance of different metrics for dynamic routing.

A Novel Construction of Complex Orthogonal Designs with Maximal Rate and Low-PAPR

Space-time block codes based on orthogonal designs are used for wireless communications with multiple transmit antennas which can achieve full transmit diversity and have low decoding complexity. However, the rate of the square real/complex orthogonal designs tends to zero with increase in number of antennas, while it is possible to have a rate-1 real orthogonal design (ROD) for any number of antennas.In case of complex orthogonal designs (CODs), rate-1 codes exist only for 1 and 2 antennas. In general, For a transmit antennas, the maximal rate of a COD is 1/2 + l/n or 1/2 + 1/n+1 for n even or odd respectively. In this paper, we present a simple construction for maximal-rate CODs for any number of antennas from square CODs which resembles the construction of rate-1 RODs from square RODs. These designs are shown to be amenable for construction of a class of generalized CODs (called Coordinate-Interleaved Scaled CODs) with low peak-to-average power ratio (PAPR) having the same parameters as the maximal-rate codes. Simulation results indicate that these codes perform better than the existing maximal rate codes under peak power constraint while performing the same under average power constraint.

High-Rate,2-Group ML-Decodable STBCs for 2(m) Transmit Antennas

A Space-Time Block Code (STBC) in K-variables is said to be g-Group ML-Decodable (GMLD) if its Maximum-Likelihood (ML) decoding metric can be written as a sum of g independent terms, with each term being a function of a subset of the K variables. In this paper, a construction method to obtain high-rate, 2-GMLD STBCs for 2(m) transmit antennas, m > 1, is presented. The rate of the STBC obtained for 2(m) transmit antennas is 2(m-2) + 1/2(m), complex symbols per channel use. The design method is illustrated for the case of 4 and 8 transmit antennas. The code obtained for 4 transmit antennas is equivalent to the rate-5/4 Quasi-Orthogonal design (QOD) proposed by Yuen, Guan and Tjung.

High Rate Capability of a Dual-Porosity LiFePO4/C Composite

Mesoporous intercalation compounds consisting of two differentdistributions of pores represent a potentially attractive material for high-rate cathodes. A mesoporous LiFePO4/C composite with two sizes of pores is prepared for the first time via a solution-based polymer templating technique. The precursor of the LiFePO4/C composite is heated at different temperatures in the range from 600 to 800 degrees C to study the effect of crystallinity, porosity, and morphology on the electrochemical performance. The composite is found to attain reduction in the surface area, carbon content, and porosity upon increasing temperature. Nonetheless, the composite prepared at 700 degrees C with pore-size distributions of around 4 and 50 nm exhibits a high rate capability and stable capacity retention upon cycling.

Nonlinear measures of heart rate time series: influence of posture and controlled breathing

In this study, we investigated measures of nonlinear dynamics and chaos theory in regards to heart rate variability in 27 normal control subjects in supine and standing postures, and 14 subjects in spontaneous and controlled breathing conditions. We examined minimum embedding dimension (MED), largest Lyapunov exponent (LLE) and measures of nonlinearity (NL) of heart rate time series. MED quantifies the system's complexity, LLE predictability and NL, a measure of deviation from linear processes. There was a significant decrease in complexity (P<0.00001), a decrease in predictability (P<0.00001) and an increase in nonlinearity (P=0.00001) during the change from supine to standing posture. Decrease in MED, and increases in NL score and LLE in standing posture appear to be partly due to an increase in sympathetic activity of the autonomous nervous system in standing posture. An improvement in predictability during controlled breathing appears to be due to the introduction of a periodic component. (C) 2000 published by Elsevier Science B.V.

The effect of cooling rate on the structure and properties of closed-cell aluminium foams

The application of different cooling rates as a strategy to enhance the structure of aluminium foams is studied. The potential to influence the level of morphological defects and cell size non-uniformities is investigated. AlSi6Cu4 alloy was foamed through the powder compact route and then solidified, applying three different cooling rates. Foam development was monitored in situ by means of X-ray radioscopy while foaming inside a closed mould. The macro-structure of the foams was analysed in terms of cell size distribution as determined by X-ray tomography. Compression tests were conducted to assess the mechanical performance of the foams and measured properties were correlated with structural features of the foams. Moreover, possible changes in the ductile brittle nature of deformation with cooling rate were analysed by studying the initial stages of deformation. We observed improvements in the cell size distributions, reduction in microporosity and grain size at higher cooling rates, which in turn led to a notable enhancement in compressive strength. (C) 2010 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

A Low ML-Decoding Complexity, High Coding Gain, Full-Rate, Full-Diversity STBC for 4 x 2 MIMO System

This paper proposes a full-rate, full-diversity space-time block code(STBC) with low maximum likelihood (ML) decoding complexity and high coding gain for the 4 transmit antenna, 2 receive antenna (4 x 2) multiple-input multiple-output (MIMO) system that employs 4/16-QAM. For such a system, the best code known is the DjABBA code and recently, Biglieri, Hong and Viterbo have proposed another STBC (BHV code) for 4-QAM which has lower ML-decoding complexity than the DjABBA code but does not have full-diversity like the DjABBA code. The code proposed in this paper has the same ML-decoding complexity as the BHV code for any square M-QAM but has full-diversity for 4- and 16-QAM. Compared with the DjABBA code, the proposed code has lower ML-decoding complexity for square M-QAM constellation, higher coding gain for 4- and 16-QAM, and hence a better codeword error rate (CER) performance. Simulation results confirming this are presented.

Crosstalk between the sympathetic nervous system, inflammation and coagulation in gestational diabetes; a therapeutic approach in postmenopausal hypertension

The occurrence of gestational diabetes (GDM) during pregnancy is a powerful sign of a risk of later type 2 diabetes (T2D) and cardiovascular diseases (CVDs). The physiological basis for this disease progression is not yet fully understood, but increasing evidence exists on interplay of insulin resistance, subclinical inflammation, and more recently, on unbalance of the autonomic nervous system. Since the delay in development of T2D and CVD after GDM ranges from years to decades, better understanding of the pathophysiology of GDM could give us new tools for primary prevention. The present study was aimed at investigating the role of the sympathetic nervous system (SNS) in GDM and its associations with insulin and a variety of inflammatory cytokines and coagulation and fibrinolysis markers. This thesis covers two separate study lines. Firstly, we investigated 41 women with GDM and 22 healthy pregnant and 14 non-pregnant controls during the night in hospital. Blood samples were drawn at 24:00, 4:00 and 7:00 h to determine the concentrations of plasma glucose, insulin, noradrenaline (NA) and adrenomedullin, markers of subclinical inflammation, coagulation and fibrinolysis variables and platelet function. Overnight holter ECG recording was performed for analysis of heart rate variability (HRV). Secondly, we studied 87 overweight hypertensive women with natural menopause. They were randomised to use a central sympatholytic agent, moxonidine (0.3mg twice daily), the β-blocking agent atenolol (50 mg once daily+blacebo once daily) for 8 weeks. Inflammatory markers and adiponectin were analysed at the beginning and after 8 weeks. Activation of the SNS (increase in NA, decreased HRV) was seen in pregnant vs. non-pregnant women, but no difference existed between GDM and normal pregnancy. However, modulation (internal rhythm) of HRV was attenuated in GDM. Insulin and inflammatory cytokine levels were comparable in all pregnant women but nocturnal variation of concentrations of C-reactive protein, serum amyloid A and insulin were reduced in GDM. Levels of coagulation factor VIII were lower in GDM compared with normal pregnancy, whereas no other differences were seen in coagulation and fibrinolysis markers. No significant associations were seen between NA and the studied parameters. In the study of postmenopausal women, moxonidine treatment was associated with favourable changes in the inflammatory profile, seen as a decrease in TNFα concentrations (increase in atenolol group) and preservation of adiponectin levels (decrease in atenolol group). In conclusion, our results did not support our hypotheses of increased SNS activity in GDM or a marked association between NA and inflammatory and coagulation markers. Reduced biological variation of HRV, insulin and inflammatory cytokines suggests disturbance of autonomic and hormonal regulatory mechanisms in GDM. This is a novel finding. Further understanding of the regulatory mechanisms could allow earlier detection of risk women and the possibility of prevention. In addition, our results support consideration of the SNS as one of the therapeutic targets in the battle against metabolic diseases, including T2D and CVD.