Latanoprost with high precision, piezo-print microdose delivery for IOP lowering: clinical results of the PG21 study of 0.4 µg daily microdose.

Background:Topical high-precision piezo-print delivery of microdoses of latanoprost achieved significant IOP reduction consistent with the eyedropper effect but with a 75% reduced exposure to drugs and preservatives. Prostaglandin analogs are a mainstay glaucoma therapy. However, conventional eyedroppers deliver 30-50 µL drops that greatly exceed the physiologic 7-µL ocular tear film capacity. Eyedropper overdosing floods the eye with excess drug compounds and preservatives, resulting in ocular surface toxicity, periorbitopathy, and other well-characterized ocular side effects. Piezoelectric high-precision microdosing provides targeted delivery that can reduce exposure to both drug and preservatives compared to conventional eyedropper delivery, with the potential to deliver similar biologic effect. Methods:Both eyes (N=60) of 30 healthy volunteers received single 8-µL microdoses of 0.005% latanoprost (0.4 µg; µRx-latanoprost) on the morning of Days 1 and 2 using a high-precision, piezo-print horizontal delivery system. Diurnal IOP was measured before and 2 days after microdosing. Main efficacy outcomes were diurnal IOP change after µRx-latanoprost microdosing and accurate microdosing success rates, and the primary safety outcome was adverse event (AE) incidence. Results:µRx-latanoprost reduced baseline IOP by 26% and 30% at 1 and 2 days postadministration, respectively. Successful topical dosing was achieved in 100% of technician-assisted deliveries. All patients successfully self-administered microdoses after receiving training. Microdose administration was well tolerated and did not result in any AEs. Conclusion:Microdosing of 0.4 µg of µRx-latanoprost achieved significant IOP reduction. Lower ocular exposure with topical prostaglandin analog microdosing can enable new therapeutic opportunities for optimizing glaucoma treatment. Microdosing may also be beneficial in reducing ocular side effects associated with excessive drug product and preservatives often used to treat chronic ocular diseases such as glaucoma

Large substitution boxes with efficient combinational implementations

At a fundamental level, the security of symmetric key cryptosystems ties back to Claude Shannon\u27s properties of confusion and diffusion. Confusion can be defined as the complexity of the relationship between the secret key and ciphertext, and diffusion can be defined as the degree to which the influence of a single input plaintext bit is spread throughout the resulting ciphertext. In constructions of symmetric key cryptographic primitives, confusion and diffusion are commonly realized with the application of nonlinear and linear operations, respectively. The Substitution-Permutation Network design is one such popular construction adopted by the Advanced Encryption Standard, among other block ciphers, which employs substitution boxes, or S-boxes, for nonlinear behavior. As a result, much research has been devoted to improving the cryptographic strength and implementation efficiency of S-boxes so as to prohibit cryptanalysis attacks that exploit weak constructions and enable fast and area-efficient hardware implementations on a variety of platforms. To date, most published and standardized S-boxes are bijective functions on elements of 4 or 8 bits. In this work, we explore the cryptographic properties and implementations of 8 and 16 bit S-boxes. We study the strength of these S-boxes in the context of Boolean functions and investigate area-optimized combinational hardware implementations. We then present a variety of new 8 and 16 bit S-boxes that have ideal cryptographic properties and enable low-area combinational implementations

SPACE EGGS - Satellite Coverage Model for Low Earth Orbit Constellations

The effectiveness calculations of global, regional, and area coverage for proliferated small satellite constellations in low altitude orbits stress the capability of conventional analytical techniques. A new approach that combines the Mollweide (equal area) projection with an on-screen color manipulation of the picture elements (or pixels) has been developed and utilized over the past decade. This technique enables the optimization of large satellite constellations with multiple communication or sensor viewing configurations, with a minimum number of calculations. Complex viewing geometries are well adapted with this analytical approach, along with exclusion requirements such as the sun, moon or earth avoidance. This technique has proven useful in minimizing the number of low altitude communication satellites (for any planet) and optimizing the sensor suite for specific missions

Optimizing S-box Implementations for Several Criteria using SAT Solvers

We explore the feasibility of applying SAT solvers to optimizing implementations of small functions such as S-boxes for multiple optimization criteria, e.g., the number of nonlinear gates and the number of gates. We provide optimized implementations for the S-boxes used in Ascon, ICEPOLE, Joltik/Piccolo, Keccak/Ketje/Keyak, LAC, Minalpher, PRIMATEs, Pr\o st, and RECTANGLE, most of which are candidates in the secound round of the CAESAR competition. We then suggest a new method to optimize for circuit depth and we make tooling publicly available to find efficient implementations for several criteria. Furthermore, we illustrate with the 5-bit S-box of PRIMATEs how multiple optimization criteria can be combined

Solving Circuit Optimisation Problems in Cryptography and Cryptanalysis

One of the hardest problems in computer science is the problem of gate-eficient implementation. Such optimizations are particularly important in industrial hardware implementations of standard cryptographic algorithms. In this paper we focus on optimizing some small circuits such as S-boxes in cryptographic algorithms. We consider the notion of Multiplicative Complexity studied in 2008 by Boyar and Peralta and applied to find interesting optimizations for the S-box of the AES cipher. We applied this methodology to produce a compact implementation of several ciphers. In this short paper we report our results on PRESENT and GOST, two block ciphers known for their exceptionally low hardware cost. This kind of representation seems to be very promising in implementations aiming at preventing side channel attacks on cryptographic chips such as DPA. More importantly, we postulate that this kind of minimality is also an important and interesting tool in cryptanalysis

Minimization of Bitsliced Representation of 4×4 S-Boxes based on Ternary Logic Instruction

The article is devoted to methods and tools for generating software-oriented bit-sliced descriptions of bijective 4×4 S-Boxes with a reduced number of instructions based on a ternary logical instruction. Bitsliced descriptions generated by the proposed method make it possible to improve the performance and security of software implementations of crypto-algorithms using 4×4 S-Boxes on various processor architectures. The paper develops a heuristic minimization method that uses a ternary logical instruction, which is available in ×86–64 processors with AVX-512 support and some GPU processors. Thanks to the combination of various heuristic techniques (preliminary calculations, exhaustive search to a certain depth, refinement search) in the method, it was possible to reduce the number of gates in bit-sliced descriptions of S-Boxes compared to other known methods. The corresponding software in the form of a utility in the Python language was developed and its operation was tested on 225 S-Boxes of various crypto-algorithms. It was established that the developed method generates a bit-sliced description with a smaller number of ternary instructions in 90.2% of cases, compared to the best-known method implemented in the sboxgates utility

Optimizing visual properties of game content through neuroevolution

This paper presents a search-based approach to generating game content that satisfies both gameplay requirements and user-expressed aesthetic criteria. Using evolutionary constraint satisfaction, we search for spaceships (for a space combat game) represented as compositional patternproducing networks. While the gameplay requirements are satisfied by ad-hoc defined constraints, the aesthetic evaluation function can also be informed by human aesthetic judgement. This is achieved using indirect interactive evolution, where an evaluation function re-weights an array of aesthetic criteria based on the choices of a human player. Early results show that we can create aesthetically diverse and interesting spaceships while retaining in-game functionality.peer-reviewe

Stealthy parametric hardware Trojans in VLSI Circuits

Over the last decade, hardware Trojans have gained increasing attention in academia, industry and by government agencies. In order to design reliable countermeasures, it is crucial to understand how hardware Trojans can be built in practice. This is an area that has received relatively scant treatment in the literature. In this thesis, we examine how particularly stealthy parametric Trojans can be introduced to VLSI circuits. Parametric Trojans do not require any additional logic and are purely based on subtle manipulations on the sub-transistor level to modify the parameters of few transistors which makes them very hard to detect. We introduce a design methodology to insert stealthy parametric hardware Trojans which are based on injecting extremely rare path delay faults into the netlist of the target circuit. As a case study, we apply our method to a 32-bit multiplier circuit resulting in a stealthy Trojan multiplier that computes faulty outputs for specific combinations of input pairs that are applied to the circuit. The multiplier can be used to realize bug attacks, introduced by Biham et al. in 2008. We also extend this concept and show how it can be used to attack ECDH key agreement protocols. Our method is a versatile tool for designing stealthy Trojans for a given circuit and is not restricted to multipliers and the bug attack. In this thesis we also examine how a stealthy side-channel hardware Trojan can be inserted in a provably-secure side-channel analysis protected implementation. Once the Trojan is triggered, the malicious design exhibits exploitable side-channel leakage leading to successful key recovery attacks. The underlying concept is based on a secure masked hardware implementation which does not exhibit any detectable leakage. However, by running the device at a particular clock frequency one of the requirements of the underlying masking scheme is not fulfilled anymore, and the device\u27s side-channel leakage can be exploited. We apply our technique to a Threshold Implementation of the PRESENT block cipher realized in both FPGA and ASIC. We show that triggering the Trojan makes both FPGA and ASIC prototypes vulnerable to certain SCA attacks. True random number generators (TRNGs) are an essential component of cryptographic designs, which are used to generate private keys for encryption and authentication, and are used in masking countermeasures. This thesis also presents a mechanism to design a stealthy parametric hardware Trojan for ring oscillator-based TRNGs. When the Trojan is triggered by operation at a specific high temperature the malicious TRNG generates predictable non-random outputs, yet under normal operating conditions it works correctly. Also we elaborate a stochastic model based on Markov Chains by which the attacker can use their knowledge of the Trojan to predict the TRNG outputs

Optimizing Implementations of Lightweight Building Blocks

We study the synthesis of small functions used as building blocks in lightweight cryptographic designs in terms of hardware implementations. This phase most notably appears during the ASIC implementation of cryptographic primitives. The quality of this step directly affects the output circuit, and while general tools exist to carry out this task, most of them belong to proprietary software suites and apply heuristics to any size of functions. In this work, we focus on small functions (4- and 8-bit mappings) and look for their optimal implementations on a specific weighted instructions set which allows fine tuning of the technology. We propose a tool named LIGHTER, based on two related algorithms, that produces optimized implementations of small functions. To demonstrate the validity and usefulness of our tool, we applied it to two practical cases: first, linear permutations that define diffusion in most of SPN ciphers; second, non-linear 4-bit permutations that are used in many lightweight block ciphers. For linear permutations, we exhibit several new MDS diffusion matrices lighter than the state-of-the-art, and we also decrease the implementation cost of several already known MDS matrices. As for non-linear permutations, LIGHTER outperforms the area-optimized synthesis of the state-of-the-art academic tool ABC. Smaller circuits can also be reached when ABC and LIGHTER are used jointly

Shorter Linear Straight-Line Programs for MDS Matrices

Recently a lot of attention is paid to the search for efficiently implementable MDS matrices for lightweight symmetric primitives. Previous work concentrated on locally optimizing the multiplication with single matrix elements. Separate from this line of work, several heuristics were developed to find shortest linear straight-line programs. Solving this problem actually corresponds to globally optimizing multiplications by matrices. In this work we combine those, so far largely independent line of works. As a result, we achieve implementations of known, locally optimized, and new MDS matrices that significantly outperform all implementations from the literature. Interestingly, almost all previous locally optimized constructions behave very similar with respect to the globally optimized implementation. As a side effect, our work reveals the so far best implementation of the AES MixColumns operation with respect to the number of XOR operations needed