Estimating training data boundaries in surrogate-based modeling

Using surrogate models outside training data boundaries can be risky and subject to significant errors. This paper presents a computationally efficient approach to estimate the boundaries of training data inputs in surrogate modeling using the Mahalanobis distance (MD). This distance can then be used as a threshold for deciding whether or not a particular prediction site is within the boundaries of the training data inputs, and has the potential of a likelihood/probabilistic interpretation. The approach is evaluated using two and four dimensional analytical restricted input spaces and a complex biomechanical six dimensional problem. The proposed approach: i) gives good approximations for the boundaries of the restricted input spaces, ii) exhibits reasonable error rates when classifying prediction sites as inside or outside known restricted input spaces and iii) reflects expected error trends for increasing values of the MDs similar to those obtained using a computationally expensive convex hull approach.     

Keyword guessing attacks on secure searchable public key encryption schemes with a designated tester

The first searchable public key encryption scheme with designated testers (dPEKS) known to be secure against keyword guessing attacks was due to Rhee et al. [H.S. Rhee, W. Susilo, and H.J. Kim, Secure searchable public key encryption scheme against keyword guessing attacks, IEICE Electron. Express 6(5) (2009), pp. 237–243]. Recently, some dPEKS schemes, including the Rhee et al. scheme, were found to be vulnerable to keyword guessing attacks by a malicious server. However, the Rhee et al. dPEKS scheme and its improved variants are still known to be secure against keyword guessing attack by the outsider attacker to date. In this paper, we present a keyword guessing attack by the outsider attacker on the existing dPEKS schemes. We first describe the attack scenario which is possible in the current nature of the Internet and public key encryption with keyword search applications, e.g. email routing. We then demonstrate the detailed attack steps on the Rhee et al. scheme as an attack instance. We emphasize that our attack is generic and it equally applies to all existing dPEKS schemes that claim to be secure against keyword guessing attacks by the outsider attacker.     

The Rocky Road from Preclinical Findings to Successful Targeted Therapy in Pleural Mesothelioma

Pleural mesothelioma (PM) is a rare and aggressive disease that arises from the mesothelial cells lining the pleural cavity. Approximately 80% of PM patients have a history of asbestos exposure. The long latency period of 20–40 years from the time of asbestos exposure to diagnosis, suggests that multiple somatic genetic alterations are required for the tumorigenesis of PM. The genomic landscape of PM has been characterized by inter- and intratumor heterogeneity associated with the impairment of tumor suppressor genes such as CDKN2A, NF2, and BAP1. Current systemic therapies have shown only limited efficacy, and none is approved for patients with relapsed PM. Advances in understanding of the molecular landscape of PM has facilitated several biomarker-driven clinical trials but so far, no predictive biomarkers for targeted therapies are in clinical use. Recent advances in the PM genetics have provided optimism for successful molecular strategies in the future. Here, we summarize the molecular mechanism underlying PM pathogenesis and review potential therapeutic targets.     

Laser-Induced,Green and Biocompatible Paper-Based Devices for Circular Electronics

The growing usage and consumption of electronics-integrated items into the daily routine has raised concerns on the disposal and proper recycling of these components. Here, a fully sustainable and green technology for the fabrication of different electronics on fruit-waste derived paper substrate, is reported. The process relies on the carbonization of the topmost surface of different cellulose-based substrates, derived from apple-, kiwi-, and grape-based processes, by a CO₂ laser. By optimizing the lasing parameters, electronic devices, such as capacitors, biosensors, and electrodes for food monitoring as well as heart and respiration activity analysis, are realized. Biocompatibility tests on fruit-based cellulose reveal no shortcoming for on-skin applications. The employment of such natural and plastic-free substrate allows twofold strategies for electronics recycling. As a first approach, device dissolution is achieved at room temperature within 40 days, revealing transient behavior in natural solution and leaving no harmful residuals. Alternatively, the cellulose-based electronics is reintroduced in nature, as possible support for plant seeding and growth or even soil amendment. These results demonstrate the realization of green, low-cost and circular electronics, with possible applications in smart agriculture and the Internet-of-Thing, with no waste creation and zero or even positive impact on the ecosystem.     

Carrier Localization on the Nanometer-Scale limits Transport in Metal Oxide Photoabsorbers

Metal oxides are considered as stable and low-cost photoelectrode candidates for hydrogen production by photoelectrochemical solar water splitting. However, their power conversion efficiencies usually suffer from poor transport of photogenerated charge carriers, which has been attributed previously to a variety of effects occurring on different time and length scales. In search for common understanding and for a better photo-conducting metal oxide photoabsorber, CuFeO₂, α-SnWO₄, BaSnO₃, FeVO₄, CuBi₂O₄, α-Fe₂O₃, and BiVO₄ are compared. Their kinetics of thermalization, trapping, localization, and recombination are monitored continuously 100 fs–100 µs and mobilities are determined for different probing lengths by combined time-resolved terahertz and microwave spectroscopy. As common issue, we find small mobilities < 3 cm²V^-1s^-1. Partial carrier localization further slows carrier diffusion beyond localization lengths of 1–6 nm and explains the extraordinarily long conductivity tails, which should not be taken as a sign of long diffusion lengths. For CuFeO₂, the localization is attributed to electrostatic barriers that enclose the crystallographic domains. The most promising novel material is BaSnO₃, which exhibits the highest mobility after reducing carrier localization by annealing in H₂. Such overcoming of carrier localization should be an objective of future efforts to enhance charge transport in metal oxides.     

Molecular Engineering of Cyclic Azobenzene-Peptide Hybrid Ligands for the Purification of Human Blood Factor VIII via Photo-Affinity Chromatography

The use of benign stimuli to control the binding and release of labile biologics for their isolation from complex feedstocks is a key goal of modern biopharmaceutical technology. This study introduces cyclic azobenzene-peptide (CAP) ligands for the rapid and discrete photo-responsive capture and release of blood coagulation factor VIII (FVIII). A predictive method—based on amino acid sequence and molecular architecture of CAPs—is developed to correlate the conformation of cis/trans-CAP photo-isomers to FVIII binding and release. Combined in silico - in vitro analysis of FVIII:peptide interactions guide the design of a rational approach to optimize isomerization kinetics and biorecognition of CAPs. A photoaffinity adsorbent, prepared by conjugating selected CAP G-cyclo_AZOB[Lys-YYKHLYN-Lys]-G on translucent chromatographic beads, features high binding capacity (>6 mg of FVIII per mL of resin) and rapid photo-isomerization kinetics (τ < 30 s) when exposed to 420–450 nm light at the intensity of 0.1 W cm⁻². The adsorbent purifies FVIII from a recombinant harvest using a single mobile phase, affording high product yield (>90%), purity (>95%), and blood clotting activity. The CAPs introduced in this report demonstrate a novel route integrating gentle operational conditions in a rapid and efficient bioprocess for the purification of life-saving biotherapeutics.