Improving Connectionist Energy Minimization

Symmetric networks designed for energy minimization such as Boltzman machines and Hopfield nets are frequently investigated for use in optimization, constraint satisfaction and approximation of NP-hard problems. Nevertheless, finding a global solution (i.e., a global minimum for the energy function) is not guaranteed and even a local solution may take an exponential number of steps. We propose an improvement to the standard local activation function used for such networks. The improved algorithm guarantees that a global minimum is found in linear time for tree-like subnetworks. The algorithm, called activate, is uniform and does not assume that the network is tree-like. It can identify tree-like subnetworks even in cyclic topologies (arbitrary networks) and avoid local minima along these trees. For acyclic networks, the algorithm is guaranteed to converge to a global minimum from any initial state of the system (self-stabilization) and remains correct under various types of schedulers. On the negative side, we show that in the presence of cycles, no uniform algorithm exists that guarantees optimality even under a sequential asynchronous scheduler. An asynchronous scheduler can activate only one unit at a time while a synchronous scheduler can activate any number of units in a single time step. In addition, no uniform algorithm exists to optimize even acyclic networks when the scheduler is synchronous. Finally, we show how the algorithm can be improved using the cycle-cutset scheme. The general algorithm, called activate-with-cutset, improves over activate and has some performance guarantees that are related to the size of the network's cycle-cutset.Comment: See http://www.jair.org/ for any accompanying file

Linear Complexity Private Set Intersection for Secure Two-Party Protocols

In this paper, we propose a new private set intersection (PSI) protocol with bi-oblivious data transfer that computes the following functionality. One of the parties $P_1$ inputs a set of items $X$ and a set of data pairs $D_1 = \{ (d_0^j,d_1^j)\}$ and the other party $P_2$ inputs a set of items $Y$. While $P_1$ outputs nothing, $P_2$ outputs a set of data $D_2 = \{ d_{b_j}^j \mid b_j \in \{0,1\}\}$ dependent on the intersection of $X$ and $Y$. This functionality is generally required when the PSI protocol is used as a part of a larger secure two-party secure computation such as threshold PSI or any function of the whole intersecting set in general. Pinkas et al. presented a PSI protocol at Eurocrypt 2019 for this type of functionality, which has linear complexity only in communication. While there are PSI protocols with linear computation and communication complexities in the classical PSI setting where the intersection itself is revealed to one party, to the best of our knowledge, there is no PSI protocol, which outputs a function of the membership results and satisfies linear complexity in both communication and computation. We present the first PSI protocol that outputs only a function of the membership results with linear communication and computation complexities. While creating the protocol, as a side contribution, we provide a one-time batch oblivious programmable pseudo-random function based on garbled Bloom filters. We also implemented our protocol and provide performance results

Catalic: Delegated PSI Cardinality with Applications to Contact Tracing

Private Set Intersection Cardinality (PSI-CA) allows two parties, each holding a set of items, to learn the size of the intersection of those sets without revealing any additional information. To the best of our knowledge, this work presents the first protocol that allows one of the parties to delegate PSI-CA computation to untrusted servers. At the heart of our delegated PSI-CA protocol is a new oblivious distributed key PRF (Odk-PRF) abstraction, which may be of independent interest. We explore in detail how to use our delegated PSI-CA protocol to perform privacy-preserving contact tracing. It has been estimated that a significant percentage of a given population would need to use a contact tracing app to stop a disease’s spread. Prior privacy-preserving contact tracing systems, however, impose heavy bandwidth or computational demands on client devices. These demands present an economic disincentive to participate for end users who may be billed per MB by their mobile data plan or for users who want to save battery life. We propose Catalic (ContAct TrAcing for LIghtweight Clients), a new contact tracing system that minimizes bandwidth cost and computation workload on client devices. By applying our new delegated PSI-CA protocol, Catalic shifts most of the client-side computation of contact tracing to untrusted servers, and potentially saves each user hundreds of megabytes of mobile data per day while preserving privacy

Human With No Lysine Kinase 3 (WNK3): A Target Enabling Package (TEP)

The Target Enabling Package (TEP) programme's foundation is built upon the recognition that genetic data is proving to be a powerful tool for target validation. As such, TEPs provide a critical mass of reagents and knowledge on a protein target to allow rapid biochemical and chemical exploration and characterisation of proteins with genetic linkage to key disease areas. TEPs provide an answer to the missing link between genomics and chemical biology, provide a starting point for chemical probe generation and therefore catalyse new biology and disease understanding with the ultimate aim of enabling translation collaborations and target/ drug discovery. We are committed to generating and making available 24 high-quality TEPs by June 2020.SUMMARY OF PROJECT Kinases WNK1-4 regulate cation-chloride cotransporters via phosphorylation of SPAK and OSR1 and thereby control salt homeostasis, cell volume and blood pressure. Gain of function mutations in WNK kinases are found in Gordon’s hypertension syndrome suggesting the WNK pathway as a therapeutic target. WNK3 inhibition in particular has also been shown to reduce cerebral injury after Ischemic stroke. Here we present assays and crystal structures that define (i) the molecular basis for disease mutations; (ii) the multiple functional domains of WNK kinases and their protein interactions; (iii) the binding of small molecule kinase inhibitors and a potential allosteric pocket.The work performed at the SGC has been funded by a grant from the Wellcome [106169/ZZ14/Z]

PSI from PaXoS: Fast, Malicious Private Set Intersection

We present a 2-party private set intersection (PSI) protocol which provides security against malicious participants, yet is almost as fast as the fastest known semi-honest PSI protocol of Kolesnikov et al. (CCS 2016). Our protocol is based on a new approach for two-party PSI, which can be instantiated to provide security against either malicious or semi-honest adversaries. The protocol is unique in that the only difference between the semi-honest and malicious versions is an instantiation with different parameters for a linear error-correction code. It is also the first PSI protocol which is concretely efficient while having linear communication and security against malicious adversaries, while running in the OT-hybrid model (assuming a non-programmable random oracle). State of the art semi-honest PSI protocols take advantage of cuckoo hashing, but it has proven a challenge to use cuckoo hashing for malicious security. Our protocol is the first to use cuckoo hashing for malicious-secure PSI. We do so via a new data structure, called a probe-and-XOR of strings (PaXoS), which may be of independent interest. This abstraction captures important properties of previous data structures, most notably garbled Bloom filters. While an encoding by a garbled Bloom filter is larger by a factor of $O(\lambda)$ than the original data, we describe a significantly improved PaXoS based on cuckoo hashing that achieves constant rate while being no worse in other relevant efficiency measures

Improved Private Set Intersection against Malicious Adversaries

Private set intersection (PSI) refers to a special case of secure two-party computation in which the parties each have a set of items and compute the intersection of these sets without revealing any additional information. In this paper we present improvements to practical PSI providing security in the presence of {\em malicious} adversaries. Our starting point is the protocol of Dong, Chen \& Wen (CCS 2013) that is based on Bloom filters. We identify a bug in their malicious-secure variant and show how to fix it using a cut-and-choose approach that has low overhead while simultaneously avoiding one the main computational bottleneck in their original protocol. We also point out some subtleties that arise when using Bloom filters in malicious-secure cryptographic protocols. We have implemented our PSI protocols and report on its performance. Our improvements reduce the cost of Dong et al.\u27s protocol by a factor of $14-110\times$ on a single thread. When compared to the previous fastest protocol of De Cristofaro et al., we improve the running time by $8-24\times$. For instance, our protocol has an online time of 14 seconds and an overall time of 2.1 minutes to securely compute the intersection of two sets of 1 million items each

Sub-logarithmic Distributed Oblivious RAM with Small Block Size

Oblivious RAM (ORAM) is a cryptographic primitive that allows a client to securely execute RAM programs over data that is stored in an untrusted server. Distributed Oblivious RAM is a variant of ORAM, where the data is stored in $m>1$ servers. Extensive research over the last few decades have succeeded to reduce the bandwidth overhead of ORAM schemes, both in the single-server and the multi-server setting, from $O(\sqrt{N})$ to $O(1)$. However, all known protocols that achieve a sub-logarithmic overhead either require heavy server-side computation (e.g. homomorphic encryption), or a large block size of at least $\Omega(\log^3 N)$. In this paper, we present a family of distributed ORAM constructions that follow the hierarchical approach of Goldreich and Ostrovsky [GO96]. We enhance known techniques, and develop new ones, to take better advantage of the existence of multiple servers. By plugging efficient known hashing schemes in our constructions, we get the following results: 1. For any $m\geq 2$, we show an $m$-server ORAM scheme with $O(\log N/\log\log N)$ overhead, and block size $\Omega(\log^2 N)$. This scheme is private even against an $(m-1)$-server collusion. 2. A 3-server ORAM construction with $O(\omega(1)\log N/\log\log N)$ overhead and a block size almost logarithmic, i.e. $\Omega(\log^{1+\epsilon}N)$. We also investigate a model where the servers are allowed to perform a linear amount of light local computations, and show that constant overhead is achievable in this model, through a simple four-server ORAM protocol

Neuregulin Promotes Incomplete Autophagy of Prostate Cancer Cells That Is Independent of mTOR Pathway Inhibition

Growth factors activating the ErbB receptors have been described in prostate tumors. The androgen dependent prostate cancer cell line, LNCaP, expresses the ErbB-1, ErbB-2 and ErbB-3 receptor tyrosine kinases. Previously, it was demonstrated that NRG activates ErbB-2/ErbB-3 heterodimers to induce LNCaP cell death, whereas, EGF activates ErbB-1/ErbB-1 or ErbB-1/ErbB-2 dimers to induce cell growth and survival. It was also demonstrated that PI3K inhibitors repressed this cell death suggesting that in androgen deprived LNCaP cells, NRG activates a PI3K-dependent pathway associated with cell death.In the present study we demonstrate that NRG induces autophagy in LNCaP cells, using LC3 as a marker. However, the autophagy induced by NRG may be incomplete since p62 levels elevate. We also demonstrated that NRG- induced autophagy is independent of mammalian target of rapamycin (mTOR) inhibition since NRG induces Akt and S6K activation. Interestingly, inhibition of reactive oxygen species (ROS) by N-acetylcysteine (NAC), inhibited NRG-induced autophagy and cell death. Our study also identified JNK and Beclin 1 as important components in NRG-induced autophagy and cell death. NRG induced elevation in JNK phosphorylation that was inhibited by NAC. Moreover, inhibitor of JNK inhibited NRG-induced autophagy and cell death. Also, in cells overexpressing Bcl-2 or cells expressing sh-RNA against Beclin 1, the effects of NRG, namely induction of autophagy and cell death, were inhibited.Thus, in LNCaP cells, NRG-induces incomplete autophagy and cell death that depend on ROS levels. These effects of NRG are mediated by signaling pathway that activates JNK and Beclin 1, but is independent of mTOR inhibition

Tyrosine kinase signalling in breast cancer

Cells are continuously exposed to diverse stimuli ranging from soluble endocrine and paracrine factors to signalling molecules on neighbouring cells. Receptors of the tyrosine kinase family play an important role in the integration and interpretation of these external stimuli, allowing a cell to respond appropriately to its environment. The activation of receptor tyrosine kinases (RTKs) is tightly controlled, allowing a normal cell to correctly integrate its external environment with internal signal transduction pathways. In contrast, due to numerous molecular alterations arising during the course of malignancy, a tumour is characterized by an abnormal response to its environment, which allows cancer cells to evade the normal mechanisms controlling cellular proliferation. Alterations in the expression of various RTKs, in their activation, and in the signalling molecules lying downstream of the receptors play important roles in the development of cancer. This topic is the major focus of the thematic review section of this issue of Breast Cancer Research