Linear Equivalence of Block Ciphers with Partial Non-Linear Layers: Application to LowMC

LowMC is a block cipher family designed in 2015 by Albrecht et al. It is optimized for practical instantiations of multi-party computation, fully homomorphic encryption, and zero-knowledge proofs. LowMC is used in the Picnic signature scheme, submitted to NIST\u27s post-quantum standardization project and is a substantial building block in other novel post-quantum cryptosystems. Many LowMC instances use a relatively recent design strategy (initiated by Gérard et al. at CHES 2013) of applying the non-linear layer to only a part of the state in each round, where the shortage of non-linear operations is partially compensated by heavy linear algebra. Since the high linear algebra complexity has been a bottleneck in several applications, one of the open questions raised by the designers was to reduce it, without introducing additional non-linear operations (or compromising security). In this paper, we consider LowMC instances with block size $n$, partial non-linear layers of size $s \leq n$ and $r$ encryption rounds. We redesign LowMC\u27s linear components in a way that preserves its specification, yet improves LowMC\u27s performance in essentially every aspect. Most of our optimizations are applicable to all SP-networks with partial non-linear layers and shed new light on this relatively new design methodology. Our main result shows that when $s < n$, each LowMC instance belongs to a large class of equivalent instances that differ in their linear layers. We then select a representative instance from this class for which encryption (and decryption) can be implemented much more efficiently than for an arbitrary instance. This yields a new encryption algorithm that is equivalent to the standard one, but reduces the evaluation time and storage of the linear layers from $r \cdot n^2$ bits to about $r \cdot n^2 - (r-1)(n-s)^2$. Additionally, we reduce the size of LowMC\u27s round keys and constants and optimize its key schedule and instance generation algorithms. All of these optimizations give substantial improvements for small $s$ and a reasonable choice of $r$. Finally, we formalize the notion of linear equivalence of block ciphers and prove the optimality of some of our results. Comprehensive benchmarking of our optimizations in various LowMC applications (such as Picnic) reveals improvements by factors that typically range between $2$x and $40$x in runtime and memory consumption

Evaluating model outputs using integrated global speleothem records of climate change since the last glacial

Although quantitative isotope data from speleothems has been used to evaluate isotope-enabled model simulations, currently no consensus exists regarding the most appropriate methodology through which to achieve this. A number of modelling groups will be running isotope-enabled palaeoclimate simulations in the framework of the Coupled Model Intercomparison Project Phase 6, so it is timely to evaluate different approaches to using the speleothem data for data–model comparisons. Here, we illustrate this using 456 globally distributed speleothem δ18O records from an updated version of the Speleothem Isotopes Synthesis and Analysis (SISAL) database and palaeoclimate simulations generated using the ECHAM5-wiso isotope-enabled atmospheric circulation model. We show that the SISAL records reproduce the first-order spatial patterns of isotopic variability in the modern day, strongly supporting the application of this dataset for evaluating model-derived isotope variability into the past. However, the discontinuous nature of many speleothem records complicates the process of procuring large numbers of records if data–model comparisons are made using the traditional approach of comparing anomalies between a control period and a given palaeoclimate experiment. To circumvent this issue, we illustrate techniques through which the absolute isotope values during any time period could be used for model evaluation. Specifically, we show that speleothem isotope records allow an assessment of a model's ability to simulate spatial isotopic trends. Our analyses provide a protocol for using speleothem isotope data for model evaluation, including screening the observations to take into account the impact of speleothem mineralogy on δ18O values, the optimum period for the modern observational baseline and the selection of an appropriate time window for creating means of the isotope data for palaeo-time-slices

MicroRNA-mediated drug resistance in breast cancer

Chemoresistance is one of the major hurdles to overcome for the successful treatment of breast cancer. At present, there are several mechanisms proposed to explain drug resistance to chemotherapeutic agents, including decreased intracellular drug concentrations, mediated by drug transporters and metabolic enzymes; impaired cellular responses that affect cell cycle arrest, apoptosis, and DNA repair; the induction of signaling pathways that promote the progression of cancer cell populations; perturbations in DNA methylation and histone modifications; and alterations in the availability of drug targets. Both genetic and epigenetic theories have been put forward to explain the mechanisms of drug resistance. Recently, a small non-coding class of RNAs, known as microRNAs, has been identified as master regulators of key genes implicated in mechanisms of chemoresistance. This article reviews the role of microRNAs in regulating chemoresistance and highlights potential therapeutic targets for reversing miRNA-mediated drug resistance. In the future, microRNA-based treatments, in combination with traditional chemotherapy, may be a new strategy for the clinical management of drug-resistant breast cancers

Viscum album L. extracts in breast and gynaecological cancers: a systematic review of clinical and preclinical research

<p>Abstract</p> <p>Background</p> <p><it>Viscum album </it>L. extracts (VAE, European mistletoe) are a widely used medicinal plant extract in gynaecological and breast-cancer treatment.</p> <p>Methods</p> <p>Systematic review to evaluate clinical studies and preclinical research on the therapeutic effectiveness and biological effects of VAE on gynaecological and breast cancer. Search of databases, reference lists and expert consultations. Criteria-based assessment of methodological study quality.</p> <p>Results</p> <p>19 randomized (RCT), 16 non-randomized (non-RCT) controlled studies, and 11 single-arm cohort studies were identified that investigated VAE treatment of breast or gynaecological cancer. They included 2420, 6399 and 1130 patients respectively. 8 RCTs and 8 non-RCTs were embedded in the same large epidemiological cohort study. 9 RCTs and 13 non-RCTs assessed survival; 12 reported a statistically significant benefit, the others either a trend or no difference. 3 RCTs and 6 non-RCTs assessed tumour behaviour (remission or time to relapse); 3 reported statistically significant benefit, the others either a trend, no difference or mixed results. Quality of life (QoL) and tolerability of chemotherapy, radiotherapy or surgery was assessed in 15 RCTs and 9 non-RCTs. 21 reported a statistically significant positive result, the others either a trend, no difference, or mixed results. Methodological quality of the studies differed substantially; some had major limitations, especially RCTs on survival and tumour behaviour had very small sample sizes. Some recent studies, however, especially on QoL were reasonably well conducted. Single-arm cohort studies investigated tumour behaviour, QoL, pharmacokinetics and safety of VAE. Tumour remission was observed after high dosage and local application. VAE application was well tolerated. 34 animal experiments investigated VAE and isolated or recombinant compounds in various breast and gynaecological cancer models in mice and rats. VAE showed increase of survival and tumour remission especially in mice, while application in rats as well as application of VAE compounds had mixed results. <it>In vitro </it>VAE and its compounds have strong cytotoxic effects on cancer cells.</p> <p>Conclusion</p> <p>VAE shows some positive effects in breast and gynaecological cancer. More research into clinical efficacy is warranted.</p