Numerical investigations of low-density nozzle flow by solving the Boltzmann equation

A two-dimensional finite-difference code to solve the BGK-Boltzmann equation has been developed. The solution procedure consists of three steps: (1) transforming the BGK-Boltzmann equation into two simultaneous partial differential equations by taking moments of the distribution function with respect to the molecular velocity u(sub z), with weighting factors 1 and u(sub z)(sup 2); (2) solving the transformed equations in the physical space based on the time-marching technique and the four-stage Runge-Kutta time integration, for a given discrete-ordinate. The Roe's second-order upwind difference scheme is used to discretize the convective terms and the collision terms are treated as source terms; and (3) using the newly calculated distribution functions at each point in the physical space to calculate the macroscopic flow parameters by the modified Gaussian quadrature formula. Repeating steps 2 and 3, the time-marching procedure stops when the convergent criteria is reached. A low-density nozzle flow field has been calculated by this newly developed code. The BGK Boltzmann solution and experimental data show excellent agreement. It demonstrated that numerical solutions of the BGK-Boltzmann equation are ready to be experimentally validated

Study of intercalation and deintercalation of Na_xCoO_2 yH_2O single crystals

Single crystals of NaxCoO2 with beta-phase (x=0.55, 0.60 and 0.65), alpha'-phase (x=0.75) and alpha-phase (x=0.9, 1.0) have been grown by the floating zone technique. The Na-extraction and hydration were carried out for the alpha'-sample to get superconducting phase of NaxCoO2.yH2O (x~0.3, y~1.3). Hydrated single crystals exhibit cracked layers perpendicular to the c-axis due to a large expansion when the water is inserted into the structure. A study of intercalation/deintercalation was performed to determine the stability of the hydrated phase and effects of hydration on the structure of the compound. X-ray diffraction and Thermogravimetric experiments are used to monitor the process of water molecules accommodated in and removed from the crystal lattice. The initial intercalation process takes place with two-water molecules corresponding to y=0.6) inserted in a formula unit, followed by a group of four (y=1.3) to form a cluster of Na(H2O)4. Thermogravimetric analysis suggests that the deintercalation occurs with the removal of the water molecules one by one from the hydrated cluster at elevated temperatures of approximately 50, 100, 200 and 300 C, respectively. Our investigations reveal that the hydration process is dynamic and that water molecule inter- and deintercalation follow different reaction paths in an irreversible way.Comment: 15 pages, 6 figures, figures with higher resolution by email request from the corresponding autho

Exhausted Plume Flow Field Prediction Near the Afterbody of Hypersonic Flight Vehicles in High Altitudes

A two-dimensional computer code to solve the Burnett equations has been developed which computes the flow interaction between an exhausted plume and hypersonic external flow near the afterbody of a flight vehicle. This Burnett-2D code extends the capability of Navier-Stokes solver (RPLUS2D code) to include high-order Burnett source terms and slip-wall conditions for velocity and temperature. Higher-order Burnett viscous stress and heat flux terms are discretized using central-differencing and treated as source terms. Blocking logic is adopted in order to overcome the difficulty of grid generation. The computation of exhaust plume flow field is divided into two steps. In the first step, the thruster nozzle exit conditions are computed which generates inflow conditions in the base area near the afterbody. Results demonstrated that at high altitudes, the computations of nozzle exit conditions must include the effects of base flow since significant expansion exists in the base region. In the second step, Burnett equations were solved for exhaust plume flow field near the afterbody. The free stream conditions are set at an altitude equal to 80km and the Mach number is equal to 5.0. The preliminary results show that the plume expansion, as altitude increases, will eventually cause upstream flow separation

Drosophila Kelch functions with Cullin-3 to organize the ring canal actin cytoskeleton

In addition to cross-linking F-actin, Drosophila Kelch is a component of a cullin-RING ubiquitin ligase complex required for morphogenesis of ring canals during oogenesis

Diurnal temperature range as a key predictor of plants’ elevation ranges globally

A prominent hypothesis in ecology is that larger species ranges are found in more variable climates because species develop broader environmental tolerances, predicting a positive range size-temperature variability relationship. However, this overlooks the extreme temperatures that variable climates impose on species, with upper or lower thermal limits more likely to be exceeded. Accordingly, we propose the ‘temperature range squeeze’ hypothesis, predicting a negative range size-temperature variability relationship. We test these contrasting predictions by relating 88,000 elevation range sizes of vascular plants in 44 mountains to short- and long-term temperature variation. Consistent with our hypothesis, we find that species’ range size is negatively correlated with diurnal temperature range. Accurate predictions of short-term temperature variation will become increasingly important for extinction risk assessment in the future.Additional co-authors: Jan-Niklas Nuppenau, Panayiotis Trigas, Jonathan P. Price, Carl A. Roland, Andreas H. Schweiger, Patrick Weigelt, Suzette G.A. Flantua and John-Arvid Gryne

Analysis of human meiotic recombination events with a parent-sibling tracing approach

<p>Abstract</p> <p>Background</p> <p>Meiotic recombination ensures that each child inherits distinct genetic materials from each parent, but the distribution of crossovers along meiotic chromosomes remains difficult to identify. In this study, we developed a parent-sibling tracing (PST) approach from previously reported methods to identify meiotic crossover sites of GEO GSE6754 data set. This approach requires only the single nucleotide polymorphism (SNP) data of the pedigrees of both parents and at least two of children.</p> <p>Results</p> <p>Compared to other SNP-based algorithms (identity by descent or pediSNP), fewer uninformative SNPs were derived with the use of PST. Analysis of a GEO GSE6754 data set containing 2,145 maternal and paternal meiotic events revealed that the pattern and distribution of paternal and maternal recombination sites vary along the chromosomes. Lower crossover rates near the centromeres were more prominent in males than in females. Based on analysis of repetitive sequences, we also showed that recombination hotspots are positively correlated with SINE/MIR repetitive elements and negatively correlated with LINE/L1 elements. The number of meiotic recombination events was positively correlated with the number of shorter tandem repeat sequences.</p> <p>Conclusions</p> <p>The advantages of the PST approach include the ability to use only two-generation pedigrees with two siblings and the ability to perform gender-specific analyses of repetitive elements and tandem repeat sequences while including fewer uninformative SNP regions in the results.</p

Targeting DNA Damage Response and Replication Stress in Pancreatic Cancer

Background and aims: Continuing recalcitrance to therapy cements pancreatic cancer (PC) as the most lethal malignancy, which is set to become the second leading cause of cancer death in our society. The study aim was to investigate the association between DNA damage response (DDR), replication stress and novel therapeutic response in PC to develop a biomarker driven therapeutic strategy targeting DDR and replication stress in PC. Methods: We interrogated the transcriptome, genome, proteome and functional characteristics of 61 novel PC patient-derived cell lines to define novel therapeutic strategies targeting DDR and replication stress. Validation was done in patient derived xenografts and human PC organoids. Results: Patient-derived cell lines faithfully recapitulate the epithelial component of pancreatic tumors including previously described molecular subtypes. Biomarkers of DDR deficiency, including a novel signature of homologous recombination deficiency, co-segregates with response to platinum (P &lt; 0.001) and PARP inhibitor therapy (P &lt; 0.001) in vitro and in vivo. We generated a novel signature of replication stress with which predicts response to ATR (P &lt; 0.018) and WEE1 inhibitor (P &lt; 0.029) treatment in both cell lines and human PC organoids. Replication stress was enriched in the squamous subtype of PC (P &lt; 0.001) but not associated with DDR deficiency. Conclusions: Replication stress and DDR deficiency are independent of each other, creating opportunities for therapy in DDR proficient PC, and post-platinum therapy

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

AI is a viable alternative to high throughput screening: a 318-target study

: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery