Cardiovascular proteomics in the era of big data: experimental and computational advances.

Proteomics plays an increasingly important role in our quest to understand cardiovascular biology. Fueled by analytical and computational advances in the past decade, proteomics applications can now go beyond merely inventorying protein species, and address sophisticated questions on cardiac physiology. The advent of massive mass spectrometry datasets has in turn led to increasing intersection between proteomics and big data science. Here we review new frontiers in technological developments and their applications to cardiovascular medicine. The impact of big data science on cardiovascular proteomics investigations and translation to medicine is highlighted

{2,2′-[o-Phenyl­enebis(nitrilo­methanylyl­idene)]diphenolato-κ4 O,N,N′,O′}nickel(II) monohydrate

The NiII atom in the title monohydrate, [Ni(C20H14N2O2)]·H2O, is coordinated within a cis-N2O2 square-planar donor set provided by the tetra­dentate Schiff base ligand. Overall, the mol­ecule has a curved shape with the dihedral angle formed between the planes of the outer benzene rings being 13.92 (18)°. The water mol­ecule was found to be disordered over two positions [ratio 0.80 (1):0.20 (1)] and the major component is linked to the complex via an O—H⋯O hydrogen bond

3-Amino-1-(3,4-dimeth­oxy­phen­yl)-9,10-dihydro­phenanthrene-2,4-dicarbonitrile

In the title compound, C24H19N3O2, the partially saturated ring adopts a distorted half-chair conformation with the methyl­ene-C atom closest to the amino­benzene ring lying 0.664 (3) Å out of the plane defined by the five remaining atoms (r.m.s. deviation = 0.1429 Å. The dihedral angle [32.01 (10)°] between the benzene rings on either side of this ring indicates a significant fold in this part of the mol­ecule. The dimeth­oxy-substituted benzene ring is almost orthogonal to the benzene ring to which it is attached [dihedral angle = 72.03 (9)°]. The mol­ecule has been observed previously as the major component of a 1:19 co-crystal with 2-amino-4-(3,4-dimeth­oxy­phen­yl)-5,6-dihydro­benzo[ha]quinoline-3-carbonitrile [Asiri et al. (2011). Acta Cryst. E67, o2873–o2873]. Supra­molecular chains with base vector [201] are formed in the crystal structure via N—H⋯O hydrogen bonds between the amino H atoms of one mol­ecule inter­acting with the meth­oxy O atoms of a neighbouring mol­ecule. The chains are linked into a three-dimensional architecture by C—H⋯π inter­actions

A second monoclinic polymorph for 3-amino-1-(4-meth­oxy­phen­yl)-9,10-dihydro­phenanthrene-2,4-dicarbonitrile

The title compound, C23H17N3O, has been previously described in a monoclinic P21/c polymorph with Z = 4 [Asiri, Al-Youbi, Faidallah, Ng & Tiekink (2011). Acta Cryst. E67, o2449]. In the new monoclinic P21/n form, with Z = 8, there are two independent mol­ecules, A and B, in the asymmetric unit. In both mol­ecules, the cyclo­hexa-1,3-diene ring has a screw-boat conformation, whereas it is a distorted half-chair in the original polymorph. There is a fold in each mol­ecule, as indicated by the dihedral angle between the benzene rings of the 1,2-dihydro­naphthalene and aniline residues of 33.19 (10)° (mol­ecule A) and 30.6 (10)° (mol­ecule B). The meth­oxy­benzene ring is twisted out of the plane of the aniline residue to which it is connected [dihedral angles = 49.22 (10) and 73.27 (10)°, in A and B respectively]. In the crystal, the two independent mol­ecules self-associate via N—H⋯N hydrogen bonds, generating a 12-membered {⋯HNC3N}2 synthon. These are connected into a supra­molecular tape in the (-101) plane by N—H⋯O(meth­oxy) inter­actions. In the P21/c polymorph, supra­molecular layers are formed by N—H⋯N and N—H⋯O inter­actions

Effects of flow-bed interactions on barrier impact

Debris flow mobility is governed by complex interactions at the flow-bed interface. These interactions may cause flow bulking and increase in momentum. Both factors need to be considered for the design of barriers installed along the flow path. In this study, channelized debris flow over a wet erodible bed impacting a terminal flexible barrier is modelled in a 28-m-long and 2-m-wide flume facility with 20o slope inclination in Hong Kong. Tests with flow volumes of 6 m3 and 9 m3 overriding both erodible and non-erodible beds are conducted. The change in normalised flow energy over the erodible bed section, the change in flow momentum and the impact dynamics on the terminal barrier is assessed

A comparative study on the indoor thermal comfort and energy consumption of typical public rental housing types under near-extreme summer conditions in Hong Kong

© 2017 The Authors. Published by Elsevier Ltd. Residents of the dense urban environment in Hong Kong suffer from poor living conditions due to building overheating, especially during near-extreme summer conditions. In this study, the thermal comfort and energy performance of typical public rental housing (PRH) building types were simulated using DesignBuilder. Results show that the oldest Slab type PRH, which has a compact building form, has the highest indoor air temperature, yet the lowest cooling energy demand. On the other hand, the Trident type PRH, with the largest external wall U-value, performs the worst overall and is the most responsive to outdoor temperature changes

Shortcomings of Vitamin D-Based Model Simulations of Seasonal Influenza

Seasonal variation in serum concentration of the vitamin D metabolite 25(OH) vitamin D [25(OH)D], which contributes to host immune function, has been hypothesized to be the underlying source of observed influenza seasonality in temperate regions. The objective of this study was to determine whether observed 25(OH)D levels could be used to simulate observed influenza infection rates. Data of mean and variance in 25(OH)D serum levels by month were obtained from the Health Professionals Follow-up Study and used to parameterize an individual-based model of influenza transmission dynamics in two regions of the United States. Simulations were compared with observed daily influenza excess mortality data. Best-fitting simulations could reproduce the observed seasonal cycle of influenza; however, these best-fit simulations were shown to be highly sensitive to stochastic processes within the model and were unable consistently to reproduce observed seasonal patterns. In this respect the simulations with the vitamin D forced model were inferior to similar modeling efforts using absolute humidity and the school calendar as seasonal forcing variables. These model results indicate it is unlikely that seasonal variations in vitamin D levels principally determine the seasonality of influenza in temperate regions

Calcium Intake and Risk of Colorectal Cancer According to Tumor-infiltrating T Cells

Calcium intake has been associated with a lower risk of colorectal cancer. Calcium signaling may enhance T-cell proliferation and differentiation, and contribute to T-cell–mediated antitumor immunity. In this prospective cohort study, we investigated the association between calcium intake and colorectal cancer risk according to tumor immunity status to provide additional insights into the role of calcium in colorectal carcinogenesis. The densities of tumor-infiltrating T-cell subsets [CD3+, CD8+, CD45RO (PTPRC)+, or FOXP3+ cell] were assessed using IHC and computer-assisted image analysis in 736 cancer cases that developed among 136,249 individuals in two cohorts. HRs and 95% confidence intervals (CI) were calculated using Cox proportional hazards regression. Total calcium intake was associated with a multivariable HR of 0.55 (comparing ≥1,200 vs. <600 mg/day; 95% CI, 0.36–0.84; Ptrend = 0.002) for CD8+ T-cell–low but not for CD8+ T-cell–high tumors (HR = 1.02; 95% CI, 0.67–1.55; Ptrend = 0.47). Similarly, the corresponding HRs (95% CIs) for calcium for low versus high T-cell–infiltrated tumors were 0.63 (0.42–0.94; Ptrend = 0.01) and 0.89 (0.58–1.35; Ptrend = 0.20) for CD3+; 0.58 (0.39–0.87; Ptrend = 0.006) and 1.04 (0.69–1.58; Ptrend = 0.54) for CD45RO+; and 0.56 (0.36–0.85; Ptrend = 0.006) and 1.10 (0.72–1.67; Ptrend = 0.47) for FOXP3+, although the differences by subtypes defined by T-cell density were not statistically significant. These potential differential associations generally appeared consistent regardless of sex, source of calcium intake, tumor location, and tumor microsatellite instability status. Our findings suggest a possible role of calcium in cancer immunoprevention via modulation of T-cell function

Unique local bone tissue characteristics in iliac crest bone biopsy from adolescent idiopathic scoliosis with severe spinal deformity

Adolescent idiopathic scoliosis is a complex disease with unclear etiopathogenesis. Systemic and persistent low bone mineral density is an independent prognostic factor for curve progression. The fundamental question of how bone quality is affected in AIS remains controversy because there is lack of site-matched control for detailed analysis on bone-related parameters. In this case-control study, trabecular bone biopsies from iliac crest were collected intra-operatively from 28 severe AIS patients and 10 matched controls with similar skeletal and sexual maturity, anthropometry and femoral neck BMD Z-score to control confounding effects. In addition to static histomorphometry, micro-computed tomography (μCT) and real time-PCR (qPCR) analyses, individual trabecula segmentation (ITS)-based analysis, finite element analysis (FEA), energy dispersive X-ray spectroscopy (EDX) were conducted to provide advanced analysis of structural, mechanical and mineralization features. μCT and histomorphometry showed consistently reduced trabecular number and connectivity. ITS revealed predominant change in trabecular rods, and EDX confirmed less mineralization. The structural and mineralization abnormality led to slight reduction in apparent modulus, which could be attributed to differential down-regulation of Runx2, and up-regulation of Spp1 and TRAP. In conclusion, this is the first comprehensive study providing direct evidence of undefined unique pathological changes at different bone hierarchical levels in AIS