499 research outputs found
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
Exploring Coral Calcification by Calcium Carbonate Overgrowth Experiments
The Scleractinia coral biomineralization process is a representative example of a heterogeneous process of nudeation and growth of biogenic CaCO3 over a mineral phase. Indeed, even if the biomineralization process starts before settlement, the bulk formation of the skeleton takes place only when the larvae attach to a solid substrate, which can be Mg-calcite from coralline algae, and the following growth proceeds on the Mg-calcite surface of the formed baseplate of the planula. Despite this peculiarity and central role of the Mg-calcite substrate, the in vitro overgrowth of CaCO3 on single crystals of Mg-calcite, or calcite, in the presence of magnesium ions and the soluble organic matrix (SOM) extracted from coral skeletons has not been performed until now. In this study, the SOMs from Stylophora pistillata and Oculina patagonica skeletons were used in a set of overgrowth experiments. The overgrown CaCO3 was characterized by microscopic, diffractometric, and spectroscopic techniques. Our results showed that CaCO3 overgrowth in the presence of S. pistillata or O. patagonica SOM produces different effects. However, there appears to be a minor distinction between samples when magnesium ions are present in solution. Moreover, the Mg-calcite substrate appears to be a favorable substrate for the overgrowth of aragonite, differently from calcite. These observations fit with the observed settling of coral larvae on Mg-calcite-based substrates and with the in vivo observation that in the planula aragonite forms on first-formed Mg-calcite crystals. The overall results of this study highlight the importance of magnesium ions, either in the solution or in the substrate, in defining the shape, morphology, and polymorphism of biodeposited CaCO3. They also suggest a magnesium-dependent biological control on the deposition of coral skeletons
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 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 on a single thread. When compared to the previous fastest protocol of De Cristofaro et al., we improve the running time by . 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
The reductive activation of CO2 across a Ti═Ti double bond: synthetic, structural, and mechanistic studies
[Image: see text] The reactivity of the bis(pentalene)dititanium double-sandwich compound Ti(2)Pn(†)(2) (1) (Pn(†) = 1,4-{Si(i)Pr(3)}(2)C(8)H(4)) with CO(2) is investigated in detail using spectroscopic, X-ray crystallographic, and computational studies. When the CO(2) reaction is performed at −78 °C, the 1:1 adduct 4 is formed, and low-temperature spectroscopic measurements are consistent with a CO(2) molecule bound symmetrically to the two Ti centers in a μ:η(2),η(2) binding mode, a structure also indicated by theory. Upon warming to room temperature the coordinated CO(2) is quantitatively reduced over a period of minutes to give the bis(oxo)-bridged dimer 2 and the dicarbonyl complex 3. In situ NMR studies indicated that this decomposition proceeds in a stepwise process via monooxo (5) and monocarbonyl (7) double-sandwich complexes, which have been independently synthesized and structurally characterized. 5 is thermally unstable with respect to a μ-O dimer in which the Ti–Ti bond has been cleaved and one pentalene ligand binds in an η(8) fashion to each of the formally Ti(III) centers. The molecular structure of 7 shows a “side-on” bound carbonyl ligand. Bonding of the double-sandwich species Ti(2)Pn(2) (Pn = C(8)H(6)) to other fragments has been investigated by density functional theory calculations and fragment analysis, providing insight into the CO(2) reaction pathway consistent with the experimentally observed intermediates. A key step in the proposed mechanism is disproportionation of a mono(oxo) di-Ti(III) species to yield di-Ti(II) and di-Ti(IV) products. 1 forms a structurally characterized, thermally stable CS(2) adduct 8 that shows symmetrical binding to the Ti(2) unit and supports the formulation of 4. The reaction of 1 with COS forms a thermally unstable complex 9 that undergoes scission to give mono(μ-S) mono(CO) species 10. Ph(3)PS is an effective sulfur transfer agent for 1, enabling the synthesis of mono(μ-S) complex 11 with a double-sandwich structure and bis(μ-S) dimer 12 in which the Ti–Ti bond has been cleaved
Feeding spectra and activity of the freshwater crab Trichodactylus kensleyi (Decapoda: Brachyura: Trichodactylidae) at La Plata basin
Background: In inland water systems, it is important to characterize the trophic links in order to identify the ‘trophic species’ and, from the studies of functional diversity, understand the dynamics of matter and energy in these environments. The aim of this study is to analyze the natural diet of Trichodactylus kensleyi of subtropical rainforest streams and corroborate the temporal variation in the trophic activity during day hours.
Results: A total of 15 major taxonomic groups were recognized in gut contents. The index of relative importance identified the following main prey items in decreasing order of importance: vegetal remains, oligochaetes, chironomid larvae, and algae. A significant difference was found in the amount of full stomachs during day hours showing a less trophic activity at midday and afternoon. The index of relative importance values evidenced the consumption of different prey according to day moments. Results of the gut content indicate that T. kensleyi is an omnivorous crab like other trichodactylid species. Opportunistic behavior is revealed by the ingestion of organisms abundant in streams such as oligochaetes and chironomid larvae. The consumption of allochthonous plant debris shows the importance of this crab as shredder in subtropical streams. However, the effective assimilation of plant matter is yet unknown in trichodactylid crabs.
Conclusions: This research provides knowledge that complements previous studies about trophic relationships of trichodactylid crabs and supported the importance of T. kensleyi in the transference of energy and matter from benthic community and riparian sources to superior trophic levels using both macro- and microfauna.Fil: Williner, Verónica. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto Nacional de Limnología. Universidad Nacional del Litoral. Instituto Nacional de Limnología; Argentina. Universidad Nacional del Litoral. Facultad de Humanidades y Ciencias; ArgentinaFil: de Azevedo Carvalho, Debora. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto Nacional de Limnología. Universidad Nacional del Litoral. Instituto Nacional de Limnología; ArgentinaFil: Collins, Pablo Agustin. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto Nacional de Limnología. Universidad Nacional del Litoral. Instituto Nacional de Limnología; Argentina. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas; Argentin
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
Combining Private Set-Intersection with Secure Two-Party Computation
Private Set-Intersection (PSI) is one of the most popular and practically relevant secure two-party computation (2PC) tasks. Therefore, designing special-purpose PSI protocols (which are more efficient than generic 2PC solutions) is a very active line of research. In particular, a recent line of work has proposed PSI protocols based on oblivious transfer (OT) which, thanks to recent advances in OT-extension techniques, is nowadays a very cheap cryptographic building block.
Unfortunately, these protocols cannot be plugged into larger 2PC applications since in these protocols one party (by design) learns the output of the intersection. Therefore, it is not possible to perform secure post-processing of the output of the PSI protocol.
In this paper we propose a novel and efficient OT-based PSI protocol that produces an encrypted output that can therefore be later used as an input to other 2PC protocols. In particular, the protocol can be used in combination with all common approaches to 2PC including garbled circuits, secret sharing and homomorphic encryption. Thus, our protocol can be combined with the right 2PC techniques to achieve more efficient protocols for computations of the form for arbitrary functions
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