Self-organized transition to coherent activity in disordered media

Synchronized oscillations are of critical functional importance in many biological systems. We show that such oscillations can arise without centralized coordination in a disordered system of electrically coupled excitable and passive cells. Increasing the coupling strength results in waves that lead to coherent periodic activity, exhibiting cluster, local and global synchronization under different conditions. Our results may explain the self-organized transition in a pregnant uterus from transient, localized activity initially to system-wide coherent excitations just before delivery.Comment: 5 pages, 4 figure

Oblivious Transfer with Constant Computational Overhead

The computational overhead of a cryptographic task is the asymptotic ratio between the computational cost of securely realizing the task and that of realizing the task with no security at all. Ishai, Kushilevitz, Ostrovsky, and Sahai (STOC 2008) showed that secure two-party computation of Boolean circuits can be realized with constant computational overhead, independent of the desired level of security, assuming the existence of an oblivious transfer (OT) protocol and a local pseudorandom generator (PRG). However, this only applies to the case of semi-honest parties. A central open question in the area is the possibility of a similar result for malicious parties. This question is open even for the simpler task of securely realizing many instances of a constant-size function, such as OT of bits. We settle the question in the affirmative for the case of OT, assuming: (1) a standard OT protocol, (2) a slightly stronger correlation-robust variant of a local PRG, and (3) a standard sparse variant of the Learning Parity with Noise (LPN) assumption. An optimized version of our construction requires fewer than 100 bit operations per party per bit-OT. For 128-bit security, this improves over the best previous protocols by 1-2 orders of magnitude. We achieve this by constructing a constant-overhead pseudorandom correlation generator (PCG) for the bit-OT correlation. Such a PCG generates $N$ pseudorandom instances of bit-OT by locally expanding short, correlated seeds. As a result, we get an end-to-end protocol for generating $N$ pseudorandom instances of bit-OT with $o(N)$ communication, $O(N)$ computation, and security that scales sub-exponentially with $N$. Finally, we present applications of our main result to realizing other secure computation tasks with constant computational overhead. These include protocols for general circuits with a relaxed notion of security against malicious parties, protocols for realizing $N$ instances of natural constant-size functions, and reducing the main open question to a potentially simpler question about fault-tolerant computation

Oblivious Transfer with constant computational overhead

The computational overhead of a cryptographic task is the asymptotic ratio between the computational cost of securely realizing the task and that of realizing the task with no security at all. Ishai, Kushilevitz, Ostrovsky, and Sahai (STOC 2008) showed that secure two-party computation of Boolean circuits can be realized with constant computational overhead, independent of the desired level of security, assuming the existence of an oblivious transfer (OT) protocol and a local pseudorandom generator (PRG). However, this only applies to the case of semi-honest parties. A central open question in the area is the possibility of a similar result for malicious parties. This question is open even for the simpler task of securely realizing many instances of a constant-size function, such as OT of bits. We settle the question in the affirmative for the case of OT, assuming: (1) a standard OT protocol, (2) a slightly stronger “correlation-robust" variant of a local PRG, and (3) a standard sparse variant of the Learning Parity with Noise (LPN) assumption. An optimized version of our construction requires fewer than 100 bit operations per party per bit-OT. For 128-bit security, this improves over the best previous protocols by 1–2 orders of magnitude. We achieve this by constructing a constant-overhead pseudorandom correlation generator (PCG) for the bit-OT correlation. Such a PCG generates N pseudorandom instances of bit-OT by locally expanding short, correlated seeds. As a result, we get an end-to-end protocol for generating N pseudorandom instances of bit-OT with o(N) communication, O(N) computation, and security that scales sub-exponentially with N. Finally, we present applications of our main result to realizing other secure computation tasks with constant computational overhead. These include protocols for general circuits with a relaxed notion of security against malicious parties, protocols for realizing N instances of natural constant-size functions, and reducing the main open question to a potentially simpler question about fault-tolerant computation

Mathematical model of a telomerase transcriptional regulatory network developed by cell-based screening: analysis of inhibitor effects and telomerase expression mechanisms

Cancer cells depend on transcription of telomerase reverse transcriptase (TERT). Many transcription factors affect TERT, though regulation occurs in context of a broader network. Network effects on telomerase regulation have not been investigated, though deeper understanding of TERT transcription requires a systems view. However, control over individual interactions in complex networks is not easily achievable. Mathematical modelling provides an attractive approach for analysis of complex systems and some models may prove useful in systems pharmacology approaches to drug discovery. In this report, we used transfection screening to test interactions among 14 TERT regulatory transcription factors and their respective promoters in ovarian cancer cells. The results were used to generate a network model of TERT transcription and to implement a dynamic Boolean model whose steady states were analysed. Modelled effects of signal transduction inhibitors successfully predicted TERT repression by Src-family inhibitor SU6656 and lack of repression by ERK inhibitor FR180204, results confirmed by RT-QPCR analysis of endogenous TERT expression in treated cells. Modelled effects of GSK3 inhibitor 6-bromoindirubin-3′-oxime (BIO) predicted unstable TERT repression dependent on noise and expression of JUN, corresponding with observations from a previous study. MYC expression is critical in TERT activation in the model, consistent with its well known function in endogenous TERT regulation. Loss of MYC caused complete TERT suppression in our model, substantially rescued only by co-suppression of AR. Interestingly expression was easily rescued under modelled Ets-factor gain of function, as occurs in TERT promoter mutation. RNAi targeting AR, JUN, MXD1, SP3, or TP53, showed that AR suppression does rescue endogenous TERT expression following MYC knockdown in these cells and SP3 or TP53 siRNA also cause partial recovery. The model therefore successfully predicted several aspects of TERT regulation including previously unknown mechanisms. An extrapolation suggests that a dominant stimulatory system may programme TERT for transcriptional stability

Intercomparison and validation of the mixed layer depth fields of global ocean syntheses

Intercomparison and evaluation of the global ocean surface mixed layer depth (MLD) fields estimated from a suite of major ocean syntheses are conducted. Compared with the reference MLDs calculated from individual profiles, MLDs calculated from monthly mean and gridded profiles show negative biases of 10–20 m in early spring related to the re-stratification process of relatively deep mixed layers. Vertical resolution of profiles also influences the MLD estimation. MLDs are underestimated by approximately 5–7 (14–16) m with the vertical resolution of 25 (50) m when the criterion of potential density exceeding the 10-m value by 0.03 kg m−3 is used for the MLD estimation. Using the larger criterion (0.125 kg m−3) generally reduces the underestimations. In addition, positive biases greater than 100 m are found in wintertime subpolar regions when MLD criteria based on temperature are used. Biases of the reanalyses are due to both model errors and errors related to differences between the assimilation methods. The result shows that these errors are partially cancelled out through the ensemble averaging. Moreover, the bias in the ensemble mean field of the reanalyses is smaller than in the observation-only analyses. This is largely attributed to comparably higher resolutions of the reanalyses. The robust reproduction of both the seasonal cycle and interannual variability by the ensemble mean of the reanalyses indicates a great potential of the ensemble mean MLD field for investigating and monitoring upper ocean processes

Interannual-decadal variability of wintertime mixed layer depths in the North Pacific detected by an ensemble of ocean syntheses

The interannual-decadal variability of the wintertime mixed layer depths (MLDs) over the North Pacific is investigated from an empirical orthogonal function (EOF) analysis of an ensemble of global ocean reanalyses. The first leading EOF mode represents the interannual MLD anomalies centered in the eastern part of the central mode water formation region in phase opposition with those in the eastern subtropics and the central Alaskan Gyre. This first EOF mode is highly correlated with the Pacific decadal oscillation index on both the interannual and decadal time scales. The second leading EOF mode represents the MLD variability in the subtropical mode water (STMW) formation region and has a good correlation with the wintertime West Pacific (WP) index with time lag of 3 years, suggesting the importance of the oceanic dynamical response to the change in the surface wind field associated with the meridional shifts of the Aleutian Low. The above MLD variabilities are in basic agreement with previous observational and modeling findings. Moreover the reanalysis ensemble provides uncertainty estimates. The interannual MLD anomalies in the first and second EOF modes are consistently represented by the individual reanalyses and the amplitudes of the variabilities generally exceed the ensemble spread of the reanalyses. Besides, the resulting MLD variability indices, spanning the 1948–2012 period, should be helpful for characterizing the North Pacific climate variability. In particular, a 6-year oscillation including the WP teleconnection pattern in the atmosphere and the oceanic MLD variability in the STMW formation region is first detected

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin