Estimating novel potential drug targets of Plasmodium falciparum by analysing the metabolic network of knock-out strains in silico

Malaria is one of the world’s most common and serious diseases causing death of about 3 million people each year. Its most severe occurrence is caused by the protozoan Plasmodium falciparum. Biomedical research could enable treating the disease by effectively and specifically targeting essential enzymes of this parasite. However, the parasite has developed resistance to existing drugsmaking it indispensable to discover new drugs. We have established a simple computational tool which analyses the topology of the metabolic network of P. falciparum to identify essential enzymes as possible drug targets.Weinvestigated the essentiality of a reaction in the metabolic network by deleting (knocking-out) such a reaction in silico. The algorithmselected neighbouring compounds of the investigated reaction that had to be produced by alternative biochemical pathways. Using breadth first searches, we tested qualitatively if these products could be generated by reactions that serve as potential deviations of the metabolic flux. With this we identified 70 essential reactions. Our results were compared with a comprehensive list of 38 targets of approved malaria drugs. When combining our approach with an in silico analysis performed recently [Yeh, I., Hanekamp, T., Tsoka, S., Karp, P.D., Altman, R.B., 2004. Computational analysis of Plasmodium falciparum metabolism: organizing genomic information to facilitate drug discovery. Genome Res. 14, 917–924] we could improve the precision of the prediction results. Finally we present a refined list of 22 new potential candidate targets for P. falciparum, half of which have reasonable evidence to be valid targets against micro-organisms and cancer

Exploring Parallelism to Improve the Performance of FrodoKEM in Hardware

FrodoKEM is a lattice-based key encapsulation mechanism, currently a semi-finalist in NIST’s post-quantum standardisation effort. A condition for these candidates is to use NIST standards for sources of randomness (i.e. seed-expanding), and as such most candidates utilise SHAKE, an XOF defined in the SHA-3 standard. However, for many of the candidates, this module is a significant implementation bottleneck. Trivium is a lightweight, ISO standard stream cipher which performs well in hardware and has been used in previous hardware designs for lattice-based cryptography. This research proposes optimised designs for FrodoKEM, concentrating on high throughput by parallelising the matrix multiplication operations within the cryptographic scheme. This process is eased by the use of Trivium due to its higher throughput and lower area consumption. The parallelisations proposed also complement the addition of first-order masking to the decapsulation module. Overall, we significantly increase the throughput of FrodoKEM; for encapsulation we see a 16 × speed-up, achieving 825 operations per second, and for decapsulation we see a 14 × speed-up, achieving 763 operations per second, compared to the previous state of the art, whilst also maintaining a similar FPGA area footprint of less than 2000 slices.</p

Sensing Subjective Well-being from Social Media

Subjective Well-being(SWB), which refers to how people experience the quality of their lives, is of great use to public policy-makers as well as economic, sociological research, etc. Traditionally, the measurement of SWB relies on time-consuming and costly self-report questionnaires. Nowadays, people are motivated to share their experiences and feelings on social media, so we propose to sense SWB from the vast user generated data on social media. By utilizing 1785 users' social media data with SWB labels, we train machine learning models that are able to "sense" individual SWB from users' social media. Our model, which attains the state-by-art prediction accuracy, can then be used to identify SWB of large population of social media users in time with very low cost.Comment: 12 pages, 1 figures, 2 tables, 10th International Conference, AMT 2014, Warsaw, Poland, August 11-14, 2014. Proceeding

Annihilation of edge dislocations in smectic A liquid crystals

This paper presents a theoretical study of the annihilation of edge dislocations in the same smectic plane in a bulk smectic-A phase. We use a time-dependent Landau-Ginzburg approach where the smectic ordering is described by the complex order parameter psi( r--&gt; ,t) =eta e(iphi) . This quantity allows both the degree of layering and the position of the layers to be monitored. We are able to follow both precollision and postcollision regimes, and distinguish different early and late behaviors within these regimes. The early precollision regime is driven by changes in the phi ( r--&gt; ) configuration. The relative velocity of the defects is approximately inversely proportional to the interdefect separation distance. In the late precollision regime the symmetry changes within the cores of defects also become influential. Following the defect collision, in the early postcollision stage, bulk layer order is approached exponentially in time. At very late times, however, there seems to be a long-time power-law tail in the order parameter fluctuation relaxation

Phase formation and high-temperature stability of very thin co-sputtered Ti-Al and multilayered Ti/Al films on thermally oxidized si substrates

Ti-Al thin films with a thickness of 200 nm were prepared either by co-sputtering from elemental Ti and Al targets or as Ti/Al multilayers with 10 and 20 nm individual layer thickness on thermally oxidized Si substrates. Some of the films were covered with a 20-nm-thick SiO2 layer, which was used as an oxidation protection against the ambient atmosphere. The films were annealed at up to 800 °C in high vacuum for 10 h, and the phase formation as well as the film architecture was analyzed by X-ray diffraction, cross section, and transmission electron microscopy, as well as Auger electron and X-ray photoelectron spectroscopy. The results reveal that the co-sputtered films remained amorphous after annealing at 600 °C independent on the presence of the SiO2 cover layer. In contrast to this, the γ-TiAl phase was formed in the multilayer films at this temperature. After annealing at 800 °C, all films were degraded completely despite the presence of the cover layer. In addition, a strong chemical reaction between the Ti and SiO2 of the cover layer and the substrate took place, resulting in the formation of Ti silicide. In the multilayer samples, this reaction already started at 600 °C

Thromboelastometry (ROTEM®) in children: age-related reference ranges and correlations with standard coagulation tests

Background The small sample volume needed and the prompt availability of results make viscoelastic methods like rotational thromboelastometry (ROTEM®) attractive for monitoring coagulation in small children. However, data on reference ranges for ROTEM® parameters in children are scarce. Methods Four hundred and seven children (ASA I and II) undergoing elective surgery were recruited for this prospective, two-centre, observational study. Subjects were grouped as follows: 0-3, 4-12, 13-24 months, 2-5, 6-10, and 11-16 yr. Study objectives were to establish age-dependent reference ranges for ROTEM® assays, analyse age dependence of parameters, and compare ROTEM® data with standard coagulation tests. Results Data from 359 subjects remained for final analysis. Except for extrinsically activated clot strength and lysis, parameters for ROTEM® assays were significantly different among all age groups. The most striking finding was that subjects aged 0-3 months exhibited accelerated initiation (ExTEM coagulation time: median 48 s, Q1-Q3 38-65 s; P=0.001) and propagation of coagulation (α angle: median 78o, Q1-Q3 69-84o; P<0.001) and maximum clot firmness (median 62 mm, Q1-Q3 54-74 mm), although standard plasma coagulation test results were prolonged (prothrombin time: median 13.2 s, Q1-Q3 12.6-13.6 s; activated partial thromboplastin time: median 42 s, Q1-Q3 40-46 s). Lysis indices of <85% were observed in nearly one-third of all children without increased bleeding tendency. Platelet count and fibrinogen levels correlated significantly with clot strength, and fibrinogen levels correlated with fibrin polymerization. Conclusions Reference ranges for ROTEM® assays were determined for all paediatric age groups. These values will be helpful when monitoring paediatric patients and in studies of perioperative coagulation in childre

A profile shape correction to reduce the vertical sensitivity of cosmic-ray neutron sensing of soil moisture

n recent years, cosmic-ray neutron sensing (CRNS) has shown a large potential among proximal sensing techniques to monitor soil moisture noninvasively, with high frequency and a large support volume (radius up to 240 m and sensing depth up to 80 cm). This signal is, however, more sensitive to closer distances and shallower depths. Inherently, CRNS-derived soil moisture is a spatially weighted value, different from an average soil moisture as retrieved by a sensor network. In this study, we systematically test a new profile shape correction on CRNS-derived soil moisture, based on additional soil moisture profile measurements and vertical unweighting, which is especially relevant during pronounced wetting or drying fronts. The analyses are conducted with data collected at four contrasting field sites, each equipped with a CRNS probe and a distributed soil moisture sensor network. After applying the profile shape correction on CRNS-derived soil moisture, it is compared with the sensor network average. Results show that the influence of the vertical sensitivity of CRNS on integral soil moisture values is successfully reduced. One to three properly located profile measurements within the CRNS support volume improve the performance. For the four investigated field sites, the RMSE decreased 11–53% when only one profile location was considered. We therefore recommend to install along with a CRNS at least one soil moisture profile in a radial distanceProfile-shape-corrected, CRNS-derived soil moisture is an unweighted integral soil moisture over the support volume, which is easier to interpret and easier to use for further applications