Recent advances in experimental techniques to probe fast excited-state dynamics in biological molecules in the gas phase : dynamics in nucleotides, amino acids and beyond

In many chemical reactions, an activation barrier must be overcome before a chemical transformation can occur. As such, understanding the behaviour of molecules in energetically excited states is critical to understanding the chemical changes that these molecules undergo. Among the most prominent reactions for mankind to understand are chemical changes that occur in our own biological molecules. A notable example is the focus towards understanding the interaction of DNA with ultraviolet radiation and the subsequent chemical changes. However, the interaction of radiation with large biological structures is highly complex, and thus the photochemistry of these systems as a whole is poorly understood. Studying the gas-phase spectroscopy and ultrafast dynamics of the building blocks of these more complex biomolecules offers the tantalizing prospect of providing a scientifically intuitive bottom-up approach, beginning with the study of the subunits of large polymeric biomolecules and monitoring the evolution in photochemistry as the complexity of the molecules is increased. While highly attractive, one of the main challenges of this approach is in transferring large, and in many cases, thermally labile molecules into vacuum. This review discusses the recent advances in cutting-edge experimental methodologies, emerging as excellent candidates for progressing this bottom-up approach

Group Leaders Optimization Algorithm

We present a new global optimization algorithm in which the influence of the leaders in social groups is used as an inspiration for the evolutionary technique which is designed into a group architecture. To demonstrate the efficiency of the method, a standard suite of single and multidimensional optimization functions along with the energies and the geometric structures of Lennard-Jones clusters are given as well as the application of the algorithm on quantum circuit design problems. We show that as an improvement over previous methods, the algorithm scales as N^2.5 for the Lennard-Jones clusters of N-particles. In addition, an efficient circuit design is shown for two qubit Grover search algorithm which is a quantum algorithm providing quadratic speed-up over the classical counterpart

Wave attenuation at a salt marsh margin: A case study of an exposed coast on the Yangtze estuary

To quantify wave attenuation by (introduced) Spartina alterniflora vegetation at an exposed macrotidal coast in the Yangtze Estuary, China, wave parameters and water depth were measured during 13 consecutive tides at nine locations ranging from 10 m seaward to 50 m landward of the low marsh edge. During this period, the incident wave height ranged from <0.1 to 1.5 m, the maximum of which is much higher than observed in other marsh areas around the world. Our measurements and calculations showed that the wave attenuation rate per unit distance was 1 to 2 magnitudes higher over the marsh than over an adjacent mudflat. Although the elevation gradient of the marsh margin was significantly higher than that of the adjacent mudflat, more than 80% of wave attenuation was ascribed to the presence of vegetation, suggesting that shoaling effects were of minor importance. On average, waves reaching the marsh were eliminated over a distance of similar to 80 m, although a marsh distance of >= 100 m was needed before the maximum height waves were fully attenuated during high tides. These attenuation distances were longer than those previously found in American salt marshes, mainly due to the macrotidal and exposed conditions at the present site. The ratio of water depth to plant height showed an inverse correlation with wave attenuation rate, indicating that plant height is a crucial factor determining the efficiency of wave attenuation. Consequently, the tall shoots of the introduced S. alterniflora makes this species much more efficient at attenuating waves than the shorter, native pioneer species in the Yangtze Estuary, and should therefore be considered as a factor in coastal management during the present era of sea-level rise and global change. We also found that wave attenuation across the salt marsh can be predicted using published models when a suitable coefficient is incorporated to account for drag, which varies in place and time due to differences in plant characteristics and abiotic conditions (i.e., bed gradient, initial water depth, and wave action).

Compositional and in Vitro Evaluation of Nonwoven Type I Collagen/Poly-dl-lactic Acid Scaffolds for Bone Regeneration

Poly-dl-lactic acid (PDLLA) was blended with type I collagen to attempt to overcome the instantaneous gelation of electrospun collagen scaffolds in biological environments. Scaffolds based on blends of type I collagen and PDLLA were investigated for material stability in cell culture conditions (37 °C; 5% CO2) in which post-electrospinning glutaraldehyde crosslinking was also applied. The resulting wet-stable webs were cultured with bone marrow stromal cells (HBMSC) for five weeks. Scanning electron microscopy (SEM), confocal laser scanning microscopy (CLSM), Fourier transform infra-red spectroscopy (FTIR) and biochemical assays were used to characterise the scaffolds and the consequent cell-scaffold constructs. To investigate any electrospinning-induced denaturation of collagen, identical PDLLA/collagen and PDLLA/gelatine blends were electrospun and their potential to promote osteogenic differentiation investigated. PDLLA/collagen blends with w/w ratios of 40/60, 60/40 and 80/20 resulted in satisfactory wet stabilities in a humid environment, although chemical crosslinking was essential to ensure long term material cell culture. Scaffolds of PDLLA/collagen at a 60:40 weight ratio provided the greatest stability over a five-week culture period. The PDLLA/collagen scaffolds promoted greater cell proliferation and osteogenic differentiation compared to HMBSCs seeded on the corresponding PDLLA/gelatine scaffolds, suggesting that any electrospinning-induced collagen denaturation did not affect material biofunctionality within 5 weeks in vitro

BodyNet: Volumetric Inference of 3D Human Body Shapes

Human shape estimation is an important task for video editing, animation and fashion industry. Predicting 3D human body shape from natural images, however, is highly challenging due to factors such as variation in human bodies, clothing and viewpoint. Prior methods addressing this problem typically attempt to fit parametric body models with certain priors on pose and shape. In this work we argue for an alternative representation and propose BodyNet, a neural network for direct inference of volumetric body shape from a single image. BodyNet is an end-to-end trainable network that benefits from (i) a volumetric 3D loss, (ii) a multi-view re-projection loss, and (iii) intermediate supervision of 2D pose, 2D body part segmentation, and 3D pose. Each of them results in performance improvement as demonstrated by our experiments. To evaluate the method, we fit the SMPL model to our network output and show state-of-the-art results on the SURREAL and Unite the People datasets, outperforming recent approaches. Besides achieving state-of-the-art performance, our method also enables volumetric body-part segmentation.Comment: Appears in: European Conference on Computer Vision 2018 (ECCV 2018). 27 page

Improved estimates of 222 nm far-UVC susceptibility for aerosolized human coronavirus via a validated high-fidelity coupled radiation-CFD code.

Transmission of SARS-CoV-2 by aerosols has played a significant role in the rapid spread of COVID-19 across the globe. Indoor environments with inadequate ventilation pose a serious infection risk. Whilst vaccines suppress transmission, they are not 100% effective and the risk from variants and new viruses always remains. Consequently, many efforts have focused on ways to disinfect air. One such method involves use of minimally hazardous 222 nm far-UVC light. Whilst a small number of controlled experimental studies have been conducted, determining the efficacy of this approach is difficult because chamber or room geometry, and the air flow within them, influences both far-UVC illumination and aerosol dwell times. Fortunately, computational multiphysics modelling allows the inadequacy of dose-averaged assessment of viral inactivation to be overcome in these complex situations. This article presents the first validation of the WYVERN radiation-CFD code for far-UVC air-disinfection against survival fraction measurements, and the first measurement-informed modelling approach to estimating far-UVC susceptibility of viruses in air. As well as demonstrating the reliability of the code, at circa 70% higher, our findings indicate that aerosolized human coronaviruses are significantly more susceptible to far-UVC than previously thought

The Radiated Energy Budget of Chromospheric Plasma in a Major Solar Flare Deduced From Multi-Wavelength Observations

This paper presents measurements of the energy radiated by the lower solar atmosphere, at optical, UV, and EUV wavelengths, during an X-class solar flare (SOL2011-02-15T01:56) in response to an injection of energy assumed to be in the form of nonthermal electrons. Hard X-ray observations from RHESSI were used to track the evolution of the parameters of the nonthermal electron distribution to reveal the total power contained in flare accelerated electrons. By integrating over the duration of the impulsive phase, the total energy contained in the nonthermal electrons was found to be $>2\times10^{31}$ erg. The response of the lower solar atmosphere was measured in the free-bound EUV continua of H I (Lyman), He I, and He II, plus the emission lines of He II at 304\AA\ and H I (Ly$\alpha$) at 1216\AA\ by SDO/EVE, the UV continua at 1600\AA\ and 1700\AA\ by SDO/AIA, and the WL continuum at 4504\AA, 5550\AA, and 6684\AA, along with the Ca II H line at 3968\AA\ using Hinode/SOT. The summed energy detected by these instruments amounted to $\sim3\times10^{30}$ erg; about 15% of the total nonthermal energy. The Ly$\alpha$ line was found to dominate the measured radiative losses. Parameters of both the driving electron distribution and the resulting chromospheric response are presented in detail to encourage the numerical modelling of flare heating for this event, to determine the depth of the solar atmosphere at which these line and continuum processes originate, and the mechanism(s) responsible for their generation.Comment: 14 pages, 18 figures. Accepted for publication in Astrophysics Journa

Decitabine impact on the endocytosis regulator RhoA, the folate carriers RFC1 and FOLR1, and the glucose transporter GLUT4 in human tumors.

BackgroundIn 31 solid tumor patients treated with the demethylating agent decitabine, we performed tumor biopsies before and after the first cycle of decitabine and used immunohistochemistry (IHC) to assess whether decitabine increased expression of various membrane transporters. Resistance to chemotherapy may arise due to promoter methylation/downregulation of expression of transporters required for drug uptake, and decitabine can reverse resistance in vitro. The endocytosis regulator RhoA, the folate carriers FOLR1 and RFC1, and the glucose transporter GLUT4 were assessed.ResultsPre-decitabine RhoA was higher in patients who had received their last therapy &gt;3&nbsp;months previously than in patients with more recent prior therapy (P = 0.02), and varied inversely with global DNA methylation as assessed by LINE1 methylation (r = -0.58, P = 0.006). Tumor RhoA scores increased with decitabine (P = 0.03), and RFC1 also increased in patients with pre-decitabine scores ≤150 (P = 0.004). Change in LINE1 methylation with decitabine did not correlate significantly with change in IHC scores for any transporter assessed. We also assessed methylation of the RFC1 gene (alias SLC19A1). SLC19A1 methylation correlated with tumor LINE1 methylation (r = 0.45, P = 0.02). There was a small (statistically insignificant) decrease in SLC19A1 methylation with decitabine, and there was a trend towards change in SLC19A1 methylation with decitabine correlating with change in LINE1 methylation (r = 0.47, P &lt;0.15). While SLC19A1 methylation did not correlate with RFC1 scores, there was a trend towards an inverse correlation between change in SLC19A1 methylation and change in RFC1 expression (r = -0.45, P = 0.19).ConclusionsIn conclusion, after decitabine administration, there was increased expression of some (but not other) transporters that may play a role in chemotherapy uptake. Larger patient numbers will be needed to define the extent to which this increased expression is associated with changes in DNA methylation

Accurate Liability Estimation Improves Power in Ascertained Case Control Studies

Linear mixed models (LMMs) have emerged as the method of choice for confounded genome-wide association studies. However, the performance of LMMs in non-randomly ascertained case-control studies deteriorates with increasing sample size. We propose a framework called LEAP (Liability Estimator As a Phenotype, https://github.com/omerwe/LEAP) that tests for association with estimated latent values corresponding to severity of phenotype, and demonstrate that this can lead to a substantial power increase

Experimental and modelling study of interaction between friction and galling under contact load change conditions

The galling process remains one of the least understood phenomena in metal forming. The transfer of material from a work-piece onto the tool surface can cause an evolutionary increase in COF and thus the use of a constant COF in FE simulations leads to progressively inaccurate results. For an aluminium work-piece, material transfer, which has history and pressure dependency, is determined by a dynamic balance between the generation and ejection of wear particles acting as a 'third body' abrasive element at the contact interface. To address this dynamic interactive phenomenon, pin-on-disc tests between AA6082 and G3500 were performed under step load change conditions. The COF evolutions, morphologies of the transfer layer and its cross-section were studied. It has been found that contact load change will disequilibrate and rebuild the dynamic balance and high load will increase the generation and ejection rate of third body and vice versa. Moreover, based on the experimental results, an interactive model was developed and presented to simulate the dynamic formation process of the aluminium third body layer under load change conditions, enabling multi-cycle simulations to model the galling distribution and friction variation